DAP12 interactions (Homo sapiens)

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Bibliography

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34. Reeve JL, Zou W, Liu Y, Maltzman JS, Ross FP, Teitelbaum SL.; ''SLP-76 couples Syk to the osteoclast cytoskeleton.''; PubMed Europe PMC Scholia
35. Zeng L, Sachdev P, Yan L, Chan JL, Trenkle T, McClelland M, Welsh J, Wang LH.; ''Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation.''; PubMed Europe PMC Scholia
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37. Brumbaugh KM, Binstadt BA, Billadeau DD, Schoon RA, Dick CJ, Ten RM, Leibson PJ.; ''Functional role for Syk tyrosine kinase in natural killer cell-mediated natural cytotoxicity.''; PubMed Europe PMC Scholia
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44. Matsuda M, Paterson HF, Rodriguez R, Fensome AC, Ellis MV, Swann K, Katan M.; ''Real time fluorescence imaging of PLC gamma translocation and its interaction with the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
45. Tomasello E, Cant C, Bühring HJ, Vély F, André P, Seiffert M, Ullrich A, Vivier E.; ''Association of signal-regulatory proteins beta with KARAP/DAP-12.''; PubMed Europe PMC Scholia
46. Tessarz AS, Cerwenka A.; ''The TREM-1/DAP12 pathway.''; PubMed Europe PMC Scholia
47. Tomasello E, Vivier E.; ''KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions.''; PubMed Europe PMC Scholia
48. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
49. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
50. Vitale M, Bottino C, Sivori S, Sanseverino L, Castriconi R, Marcenaro E, Augugliaro R, Moretta L, Moretta A.; ''NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis.''; PubMed Europe PMC Scholia
51. Angata T, Tabuchi Y, Nakamura K, Nakamura M.; ''Siglec-15: an immune system Siglec conserved throughout vertebrate evolution.''; PubMed Europe PMC Scholia
52. Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, Koretzky GA, Watson SP.; ''Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets.''; PubMed Europe PMC Scholia
53. Kim YJ, Sekiya F, Poulin B, Bae YS, Rhee SG.; ''Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2.''; PubMed Europe PMC Scholia
54. Qi Y, Martin MP, Gao X, Jacobson L, Goedert JJ, Buchbinder S, Kirk GD, O'Brien SJ, Trowsdale J, Carrington M.; ''KIR/HLA pleiotropism: protection against both HIV and opportunistic infections.''; PubMed Europe PMC Scholia
55. Colonna M.; ''TREMs in the immune system and beyond.''; PubMed Europe PMC Scholia
56. Cognet C, Farnarier C, Gauthier L, Frassati C, André P, Magérus-Chatinet A, Anfossi N, Rieux-Laucat F, Vivier E, Schleinitz N.; ''Expression of the HLA-C2-specific activating killer-cell Ig-like receptor KIR2DS1 on NK and T cells.''; PubMed Europe PMC Scholia
57. Gumá M, Busch LK, Salazar-Fontana LI, Bellosillo B, Morte C, García P, López-Botet M.; ''The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells.''; PubMed Europe PMC Scholia
58. Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE.; ''Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling.''; PubMed Europe PMC Scholia
59. Patterson RL, van Rossum DB, Nikolaidis N, Gill DL, Snyder SH.; ''Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling.''; PubMed Europe PMC Scholia
60. Todderud G, Wahl MI, Rhee SG, Carpenter G.; ''Stimulation of phospholipase C-gamma 1 membrane association by epidermal growth factor.''; PubMed Europe PMC Scholia
61. Lanier LL.; ''DAP10- and DAP12-associated receptors in innate immunity.''; PubMed Europe PMC Scholia
62. Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH.; ''Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells.''; PubMed Europe PMC Scholia
63. McVicar DW, Taylor LS, Gosselin P, Willette-Brown J, Mikhael AI, Geahlen RL, Nakamura MC, Linnemeyer P, Seaman WE, Anderson SK, Ortaldo JR, Mason LH.; ''DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase.''; PubMed Europe PMC Scholia
64. Wen R, Jou ST, Chen Y, Hoffmeyer A, Wang D.; ''Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and Fc gamma R.''; PubMed Europe PMC Scholia
65. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
66. Zou W, Reeve JL, Liu Y, Teitelbaum SL, Ross FP.; ''DAP12 couples c-Fms activation to the osteoclast cytoskeleton by recruitment of Syk.''; PubMed Europe PMC Scholia
67. Aguilar H, Alvarez-Errico D, García-Montero AC, Orfao A, Sayós J, López-Botet M.; ''Molecular characterization of a novel immune receptor restricted to the monocytic lineage.''; PubMed Europe PMC Scholia
68. Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A.; ''Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells.''; PubMed Europe PMC Scholia
69. Abe K, Rossman KL, Liu B, Ritola KD, Chiang D, Campbell SL, Burridge K, Der CJ.; ''Vav2 is an activator of Cdc42, Rac1, and RhoA.''; PubMed Europe PMC Scholia
70. Jabril-Cuenod B, Zhang C, Scharenberg AM, Paolini R, Numerof R, Beaven MA, Kinet JP.; ''Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2.''; PubMed Europe PMC Scholia
71. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
72. Call ME, Wucherpfennig KW, Chou JJ.; ''The structural basis for intramembrane assembly of an activating immunoreceptor complex.''; PubMed Europe PMC Scholia
73. Cella M, Fujikawa K, Tassi I, Kim S, Latinis K, Nishi S, Yokoyama W, Colonna M, Swat W.; ''Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity.''; PubMed Europe PMC Scholia
74. Dietrich J, Cella M, Seiffert M, Bühring HJ, Colonna M.; ''Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells.''; PubMed Europe PMC Scholia
75. Feng J, Call ME, Wucherpfennig KW.; ''The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site.''; PubMed Europe PMC Scholia
76. Cantoni C, Bottino C, Vitale M, Pessino A, Augugliaro R, Malaspina A, Parolini S, Moretta L, Moretta A, Biassoni R.; ''NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily.''; PubMed Europe PMC Scholia
77. Dinh M, Grunberger D, Ho H, Tsing SY, Shaw D, Lee S, Barnett J, Hill RJ, Swinney DC, Bradshaw JM.; ''Activation mechanism and steady state kinetics of Bruton's tyrosine kinase.''; PubMed Europe PMC Scholia
78. Bouchon A, Hernández-Munain C, Cella M, Colonna M.; ''A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.''; PubMed Europe PMC Scholia
79. Yablonski D, Kadlecek T, Weiss A.; ''Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:16761 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
B2M	Protein	P61769 (Uniprot-TrEMBL)
BTK	Protein	Q06187 (Uniprot-TrEMBL)
BTK	Protein	Q06187 (Uniprot-TrEMBL)
CD300E	Protein	Q496F6 (Uniprot-TrEMBL)
CD300E	Protein	Q496F6 (Uniprot-TrEMBL)
CD300LB	Protein	A8K4G0 (Uniprot-TrEMBL)
CD300LB	Protein	A8K4G0 (Uniprot-TrEMBL)
CD94 NKG2C HLA-E	Complex	REACT_148009 (Reactome)
CLEC5A	Protein	Q9NY25 (Uniprot-TrEMBL)
CLEC5A	Protein	Q9NY25 (Uniprot-TrEMBL)
CLM7 DAP12	Complex	REACT_147946 (Reactome)
DAG and IP3 signaling	Pathway	WP2688 (WikiPathways)	This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events.
DAP12 KIR2DS1 HLA-Cw4	Complex	REACT_148039 (Reactome)
DAP12 NKG2D	Complex	REACT_148626 (Reactome)
DAP12 NKp44	Complex	REACT_148302 (Reactome)
DAP12 TRIM2	Complex	REACT_19597 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK PI3K	Complex	REACT_148439 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK	Complex	REACT_148137 (Reactome)
DAP12 dimer MDL-1	Complex	REACT_148533 (Reactome)
DAP12 dimer TRIM1	Complex	REACT_148539 (Reactome)
DAP12 dimer	Complex	REACT_147960 (Reactome)
DAP12 receptors DAP12 dimer	Complex	REACT_147923 (Reactome)
DAP12 receptors p-DAP12 SYK	Complex	REACT_148179 (Reactome)
DAP12 receptors p-Y91,Y102-DAP12 dimer	Complex	REACT_148548 (Reactome)
FYN,LCK	Protein	REACT_148414 (Reactome)
FYN	Protein	P06241 (Uniprot-TrEMBL)
GADS SLP76	Complex	REACT_147999 (Reactome)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GRAP2	Protein	O75791 (Uniprot-TrEMBL)
GRB2-1	Protein	P62993-1 (Uniprot-TrEMBL)
GTP	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
HLA class I histocompatibility antigen, Cw-3 alpha chain precursor	Protein	P04222 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-4 alpha chain precursor	Protein	P30504 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, E alpha chain precursor	Protein	P13747 (Uniprot-TrEMBL)
HLA-Bw4 KIR3DS1 DAP12 dimer KIR3DS1 HLA-Bw4	Complex	REACT_147965 (Reactome)
HLA-C Cw4/Cw3 KIR2DS4 DAP12 dimer KIR2DS4 HLA-C Cw3/Cw4	Complex	REACT_148211 (Reactome)
HLA-C1 KIR2DS2 DAP12 dimer KIR2DS2 HLA-C1	Complex	REACT_148637 (Reactome)
HLA-E CD94 NKG2C DAP12	Complex	REACT_148264 (Reactome)
HRAS	Protein	P01112 (Uniprot-TrEMBL)
IREM2 DAP12	Complex	REACT_148241 (Reactome)
KIR2DS1 oligomer HLA-C	Complex	REACT_148177 (Reactome)
KIR2DS2 HLA-C1	Complex	REACT_148175 (Reactome)
KIR2DS2	Protein	P43631 (Uniprot-TrEMBL)
KIR2DS4 HLA-C Cw4/HLA-C Cw3	Complex	REACT_148272 (Reactome)
KIR2DS4	Protein	P43632 (Uniprot-TrEMBL)
KIR2DS5 DAP12 dimer KIR2DS5	Complex	REACT_148570 (Reactome)
KIR2DS5	Protein	Q14953 (Uniprot-TrEMBL)
KIR2DS5	Protein	Q14953 (Uniprot-TrEMBL)
KIR3DS1 HLA-Bw4	Complex	REACT_148492 (Reactome)
KIR3DS1	Protein	Q14943 (Uniprot-TrEMBL)
KLRC2	Protein	P26717 (Uniprot-TrEMBL)
KLRD1	Protein	Q13241 (Uniprot-TrEMBL)
KLRK1	Protein	P26718 (Uniprot-TrEMBL)
KRAS	Protein	P01116 (Uniprot-TrEMBL)
LAT-2	Protein	O43561-2 (Uniprot-TrEMBL)
LCK	Protein	P06239 (Uniprot-TrEMBL)
LCP2	Protein	Q13094 (Uniprot-TrEMBL)
NCR2	Protein	O95944 (Uniprot-TrEMBL)
NCR2	Protein	O95944 (Uniprot-TrEMBL)
NKG2D dimer	Complex	REACT_148030 (Reactome)
NRAS	Protein	P01111 (Uniprot-TrEMBL)
PI3K	Complex	REACT_4240 (Reactome)
PI	Metabolite	CHEBI:16618 (ChEBI)
PI	Metabolite	CHEBI:18348 (ChEBI)
PIK3CA	Protein	P42336 (Uniprot-TrEMBL)
PIK3CB	Protein	P42338 (Uniprot-TrEMBL)
PIK3R1	Protein	P27986 (Uniprot-TrEMBL)
PIK3R2	Protein	O00459 (Uniprot-TrEMBL)
PIP3 activates AKT signaling	Pathway	WP2653 (WikiPathways)	Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PLC gamma1/2	Protein	REACT_120292 (Reactome)
PLCG1	Protein	P19174 (Uniprot-TrEMBL)
PLCG2	Protein	P16885 (Uniprot-TrEMBL)
RAC1	Protein	P63000 (Uniprot-TrEMBL)
RAC1-GDP	Complex	REACT_22018 (Reactome)
RAC1-GTP	Complex	REACT_21594 (Reactome)
RAF/MAP kinase cascade	Pathway	WP2735 (WikiPathways)	The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
SIGLEC14	Protein	Q08ET2 (Uniprot-TrEMBL)
SIGLEC14/15/16 DAP12 dimer	Complex	REACT_148587 (Reactome)
SIGLEC14/15/16	Protein	REACT_148032 (Reactome)
SIGLEC15	Protein	Q6ZMC9 (Uniprot-TrEMBL)
SIGLEC16	Protein	A6NMB1 (Uniprot-TrEMBL)
SIRP beta1 DAP12	Complex	REACT_24726 (Reactome)
SIRPB1	Protein	O00241 (Uniprot-TrEMBL)
SOS1	Protein	Q07889 (Uniprot-TrEMBL)
SYK	Protein	P43405 (Uniprot-TrEMBL)
SYK	Protein	P43405 (Uniprot-TrEMBL)
TREM1	Protein	Q9NP99 (Uniprot-TrEMBL)
TREM1	Protein	Q9NP99 (Uniprot-TrEMBL)
TREM2	Protein	Q9NZC2 (Uniprot-TrEMBL)
TREM2	Protein	Q9NZC2 (Uniprot-TrEMBL)
TYROBP	Protein	O43914 (Uniprot-TrEMBL)
TYROBP	Protein	O43914 (Uniprot-TrEMBL)
VAV2	Protein	P52735 (Uniprot-TrEMBL)
VAV2/VAV3	Protein	REACT_148397 (Reactome)
VAV3	Protein	Q9UKW4 (Uniprot-TrEMBL)
class I MHC B38	Protein	Q95365 (Uniprot-TrEMBL)
p-4Y-PLCG1	Protein	P19174 (Uniprot-TrEMBL)
p-4Y-PLCG2	Protein	P16885 (Uniprot-TrEMBL)
p-5Y-LAT GRB2 SOS GADS p-3Y-SLP-76 p-2Y-BTK VAV p-PLCG	Complex	REACT_148036 (Reactome)
p-5Y-LAT GRB2 SOS GADS p-3Y-SLP-76 p-2Y-BTK VAV	Complex	REACT_148222 (Reactome)
p-5Y-LAT GRB2 SOS1 GADS p-3Y-SLP-76 PLCG VAV p-Y223,Y551-BTK	Complex	REACT_148538 (Reactome)
p-5Y-LAT GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG VAV BTK PIP3	Complex	REACT_148541 (Reactome)
p-5Y-LAT PLCG1 GADS p-3Y-SLP-76 BTK p-VAV	Complex	REACT_147977 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1 GADS SLP76 PLCG	Complex	REACT_148415 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1 GADS SLP76	Complex	REACT_148283 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG	Complex	REACT_147980 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1	Complex	REACT_148348 (Reactome)
p-5Y-LAT-2	Protein	O43561-2 (Uniprot-TrEMBL)
p-5Y-LAT-2	Protein	O43561-2 (Uniprot-TrEMBL)
p-6Y-SYK	Protein	P43405 (Uniprot-TrEMBL)
p-PLCG	Protein	REACT_160705 (Reactome)
p-SHC1 GRB2 SOS	Complex	REACT_160377 (Reactome)
p-SYK/p-BTK	Complex	REACT_148438 (Reactome)
p-Y113,Y128,Y145-LCP2	Protein	Q13094 (Uniprot-TrEMBL)
p-Y172-VAV2	Protein	P52735 (Uniprot-TrEMBL)
p-Y173-VAV3	Protein	Q9UKW4 (Uniprot-TrEMBL)
p-Y223,Y551-BTK	Protein	Q06187 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2	Protein	P29353-2 (Uniprot-TrEMBL)
p-Y91,Y102-TYROBP	Protein	O43914 (Uniprot-TrEMBL)
p21 RAS GDP	Complex	REACT_2657 (Reactome)
p21 RAS GTP	Complex	REACT_4782 (Reactome)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	ADP	Arrow	REACT_147708 (Reactome)
	ADP	Arrow	REACT_147713 (Reactome)
	ADP	Arrow	REACT_147736 (Reactome)
	ADP	Arrow	REACT_147778 (Reactome)
	ADP	Arrow	REACT_147796 (Reactome)
	ADP	Arrow	REACT_147801 (Reactome)
	ADP	Arrow	REACT_147834 (Reactome)
	ADP	Arrow	REACT_147856 (Reactome)
ATP			REACT_147708 (Reactome)
ATP			REACT_147713 (Reactome)
ATP			REACT_147736 (Reactome)
ATP			REACT_147778 (Reactome)
ATP			REACT_147796 (Reactome)
ATP			REACT_147801 (Reactome)
ATP			REACT_147834 (Reactome)
ATP			REACT_147856 (Reactome)
BTK			REACT_147785 (Reactome)
CD300E			REACT_147704 (Reactome)
CD300LB			REACT_147706 (Reactome)
CD94 NKG2C HLA-E			REACT_147751 (Reactome)
CLEC5A			REACT_147800 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK PI3K			REACT_147856 (Reactome)
	DAP12 Receptors p-DAP12 p-6Y-SYK	Arrow	REACT_147796 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK			REACT_147708 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK			REACT_147736 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK			REACT_147778 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK			REACT_147834 (Reactome)
DAP12 Receptors p-DAP12 p-6Y-SYK			REACT_147879 (Reactome)
DAP12 dimer			REACT_147704 (Reactome)
DAP12 dimer			REACT_147706 (Reactome)
DAP12 dimer			REACT_147726 (Reactome)
DAP12 dimer			REACT_147732 (Reactome)
DAP12 dimer			REACT_147742 (Reactome)
DAP12 dimer			REACT_147745 (Reactome)
DAP12 dimer			REACT_147751 (Reactome)
DAP12 dimer			REACT_147773 (Reactome)
DAP12 dimer			REACT_147777 (Reactome)
DAP12 dimer			REACT_147782 (Reactome)
DAP12 dimer			REACT_147800 (Reactome)
DAP12 dimer			REACT_147830 (Reactome)
DAP12 dimer			REACT_147866 (Reactome)
DAP12 dimer			REACT_147897 (Reactome)
DAP12 receptors DAP12 dimer			REACT_147713 (Reactome)
DAP12 receptors p-DAP12 SYK			REACT_147796 (Reactome)
	DAP12 receptors p-Y91,Y102-DAP12 dimer	Arrow	REACT_147713 (Reactome)
DAP12 receptors p-Y91,Y102-DAP12 dimer			REACT_147772 (Reactome)
FYN,LCK			REACT_147713 (Reactome)
GADS SLP76			REACT_147784 (Reactome)
	GDP	Arrow	REACT_147697 (Reactome)
	GDP	Arrow	REACT_147838 (Reactome)
GTP			REACT_147697 (Reactome)
GTP			REACT_147838 (Reactome)
KIR2DS1 oligomer HLA-C			REACT_147830 (Reactome)
KIR2DS2 HLA-C1			REACT_147777 (Reactome)
KIR2DS4 HLA-C Cw4/HLA-C Cw3			REACT_147866 (Reactome)
KIR2DS5			REACT_147742 (Reactome)
KIR3DS1 HLA-Bw4			REACT_147782 (Reactome)
LAT-2			REACT_147778 (Reactome)
NCR2			REACT_147726 (Reactome)
NKG2D dimer			REACT_147745 (Reactome)
PI3K			REACT_147879 (Reactome)
	PI	Arrow	REACT_147856 (Reactome)
PI			REACT_147785 (Reactome)
PI			REACT_147856 (Reactome)
PLC gamma1/2			REACT_147817 (Reactome)
RAC1-GDP			REACT_147838 (Reactome)
	RAC1-GTP	Arrow	REACT_147838 (Reactome)
			REACT_147697 (Reactome)	GRB2-bound SOS promotes the formation of active GTP-bound RAS. This activates the mitogen-activated protein kinase (MAPK) cascade, leading to cell growth and differentiation.
			REACT_147702 (Reactome)	Activated PLC-gamma1 disassociates from LAT. Membrane binding is crucial for PLC-gamma 1 activity. The PH-domain of PLC-gamma 1 binds to phosphatidylinositol 3,4,5-trisphosphate [PdtIns(3,4,5)P3], and is targeted to the membrane (Todderud et al. 1990, Wang & Wang. 2003, Kim et al. 2000). Activated PLCG1 then hydrolyses PIP2 to Inositol 1,4,5-triphosphate (IP3) and DAG
			REACT_147704 (Reactome)	Immune receptor expressed by myeloid cells 2 (IREM-2), is a member of the Ig-superfamily expressed on myeloid cells. The extracellular region contains a single Ig variable and a positively charged amino acid lysine in its transmembrane region followed by a short cytoplasmic tail. IREM-2 associates with activating adaptor DAP12, through the transmembrane basic amino acid residue. This association induces NFAT transcriptional activity (Aguilar et al. 2004).
			REACT_147706 (Reactome)	CLM7/TREM5 is a member of the CMRF-35/immune receptor expressed by myeloid cell (IREM) multigene family of immune receptors expressed on myeloid cells. It has a basic residue in its transmembrane domain and a functional tyrosine-based motif in its short cytoplasmic tail. This structural arrangement confers CLM7 the ability to signal through two independent pathways: one through associating with activating adaptor protein DAP12 and the other through the tyrosine motif in its cytoplasmic tail (Martinez-Barriocanal & Sayos 2006).
			REACT_147708 (Reactome)	VAV exists in an auto-inhibitory state, folded in such a way as to inhibit the GEF activity of its DH domain. This folding is mediated through binding of tyrosines in the acidic domain to the DH domain and through binding of the calponin homology (CH) domain to the C1 region. Activation of VAV may involve three events which relieve this auto-inhibition: phosphorylation of tyrosines in the acidic domain causes them to be displaced from the DH domain; binding of a ligand to the CH domain may cause it to release the C1 domain; binding of the PI3K product PIP3 to the PH domain may alter its conformation (Aghazadeh et al. 2000). VAV2/3 are phosphorylated on Y172/Y173 respectively in the acidic domain. This is mediated by SYK and Src-family tyrosine kinases (Deckert et al. 1996, Schuebel et al. 1998). Once activated, VAV2/VAV3 are involved in the activation of RAC1, PAK1, MEK and ERK.
			REACT_147713 (Reactome)	Crosslinking of receptors associated with DAP12 leads to phosphorylation of tyrosine residues in their cytoplasmic ITAM by SRC family kinases (Turnbull & Colonna 2007). This initiates downstream signaling. FYN and LCK have both been found physically and functionally associated with receptors using DAP12 signaling and have been demonstrated to be involved in DAP12 phosphorylation (Mason et al. 2006).
			REACT_147717 (Reactome)	GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). Following phosphorylation of LAT, the GRB2:SOS complex binds to the phosphorylated tyrosines and is thereby translocated to the inner face of the plasma membrane where inactive RAS:GDP resides. The three distal tyrosines, Y171, Y191 and Y226 of LAT are responsible for GRB2 association (Balagopalan et al. 2010, Zhang et al. 2000).
			REACT_147726 (Reactome)	NKp44 is a natural cytotoxicity receptor (NCR) family member selectively expressed by IL-2-activated NK cells. It is a transmembrane receptor involved in recognizing unidentified non-MHC ligands on tumor cells, mediating tumor cell lysis by activated NK cells. NKp44 is coupled to cytoplasmic signal transduction machinery via association with DAP12. Lysine-183 in the transmembrane region of NKp44 may be involved in the association with DAP12. The interaction with DAP12 influences NKp44 surface expression and hence NK cell activation (Campbell et al. 2004, Cantoni et al. 1999, Vitale et al. 1998).
			REACT_147732 (Reactome)	SIGLECs are sialic acid-recognizing receptors of the immunoglobulin (Ig) superfamily expressed on immune cells. SEGLEC14 and SEGLEC15 preferentially recognise ligands containing the glycans N-acetylneuraminic acid (Neu5Ac). SEGLEC14, SEGLEC15 and SEGLEC16 are expressed by myeloid cells and associate with the activating adapter protein DAP12 via the arginine residue in their transmembrane domains (Angata et al. 2006, Angata et al. 2007, Cao et al. 2008).
			REACT_147736 (Reactome)	SLP-76 lacks intrinsic catalytic activity and acts as a scaffold, recruiting other proteins for correct localization during molecular signal transduction (Bogin et al. 2007). Activation of DAP12-associated receptors leads to tyrosine phosphorylation of SLP-76 (Gross et al. 1999). SLP-76 has three potential tyrosine phosphorylation sites within its amino terminus region: Y113, Y128, and Y145. Phosphorylation may be mediated by SYK, analogous to the role of ZAP-70 in phosphorylating T-cell SLP-76 (Bubeck-Wardenberg et al. 1996).
			REACT_147742 (Reactome)	Killer cell immunoglobulin-like two-domain short-tail receptor 5 (KIR2DS5) is an activating KIR receptor expressed on natural killer (NK) cells and subpopulations of T lymphocytes (Nowak et al. 2010). KIR2DS5 has two Ig domains of the D1-D2 type, a short cytoplasmic tail and a positive charged transmembrane (TM) portion. No physiological ligand has yet been identified for KIR2DS5 but it is able to associate with DAP12 and induce both cytotoxicity and cytokine release when KIR2DS5 is cross-linked with monoclonal antibody (Della Chiesa et al. 2008).
			REACT_147745 (Reactome)	NKG2D is a member of the NKG2 family of C-type lectin-like surface receptors. It is a homodimeric activating receptor expressed on natural killer (NK) cells, gamma/delta T-cells and CD8+ alpha/beta T-cells. NKG2D can mediate NK activation and cytotoxicity. NKG2D interacts with the stress-induced class I like molecules MICA, MICB and ULBPs expressed on target cells. Interaction of NKG2D and NKG2D ligands leads to NK cell activation (Cosman et al. 2001, Steinle et al. 2001, Long. 2002). In mice there are two alternatively spliced isoforms of NKG2D, designated NKG2D-S and NKG2D-L. DAP12 interacts with NKG2D-S, but not NKG2D-L, whereas the DAP10 adapter associates with both NKG2D-S and NKG2D-L (Gilfillan et al. 2002, Diefenbach et al. 2002). Humans only express an NKG2D-L isoform and exclusively associate with DAP10, and not DAP12 A Structural basis for the association of DAP12 with mouse, but not human, NKG2D (Rosen et al. 2004).
			REACT_147748 (Reactome)	DAP12 is expressed as a disulfide-bonded homodimer on NK cells, myeloid cells and a subset of T cells. Cystine-7 in the extracellular domain is involved in the interchain disulphide bond (numbering according to Lanier et al. 1998).
			REACT_147751 (Reactome)	NKG2C, a C-type lectin-like surface receptor, is a member of the NKG2 family and forms heterodimers with CD94 that is expressed on NK cells and a subset of T cells. The CD94/NKG2C killer lectin-like receptor (KLR) perform an important role in immunosurveillance by binding to HLA-E complexes that present peptides derived from the signal sequences of other HLA class I molecules (A, B, C, G), thereby monitoring MHC class I expression. It has been proposed that the activating receptor CD94/NKG2C may contribute with other NK stimulatory molecules (like NKp46, NKp44 and NKp30 and NKG2D) to trigger effector functions when the control exerted by inhibitory receptors is overcome (Guma et al. 2005). NKG2C/CD94 associates with the ITAM-containing adapter protein DAP12 and this leads to cell activation and cytotoxic function. The charged residues in the transmembrane domains of DAP12 and NKG2C are necessary for this interaction (Lanier et al. 1998). NK cells expressing the CD94/NKG2C receptor are preferentially expanded during cytomegalovirus infection in humans (Lopez-Verges et al. 2011)
			REACT_147772 (Reactome)	Phosphorylated ITAM on DAP12 serves as the docking site for the two SH2 domains of SYK or ZAP70. Binding leads to SYK activation (Lanier et al. 1998, McVicar et al. 1998).
			REACT_147773 (Reactome)	TREM2 (triggering receptor expressed on myeloid cells 2 protein) is expressed on the cell membrane of a subset of myeloid cells - namely, immature dendritic cells, osteoclasts, tissue macrophages, and microglia. Like TREM1 the ligand for TREM2 is unknown. TREM2 signals through DAP12, leading to an increase in intracellular calcium and phosphorylation of ERK1/2 (Sharif & Knapp. 2008). It recognises anionic lipopolysacharides in the cell wall of bacteria and triggers the phagocytic uptake of bacteria and the release of reactive oxygen species (Neumann & Daly 2013). TREM2 on immature dendritic cells triggers upregulation of molecules involved in T cell co-stimulation such as CD86, CD40 and MHC class II, as well as up-regulation of the chemokine receptor CCR7 (Bouchon et al. 2001). In macrophages TREM2 is a negative regulator of inflammatory responses (Hamerman et al. 2006, Turnbull et al. 2006). From genome wide association studies, a TREM2 variant (encoding a substitution of arginine by histidine at residue 47 [R47H]) has been reported to be implicated in late-onset Alzheumer's disease (Neumann & Daly 2013).
			REACT_147777 (Reactome)	Killer cell immunoglobulin-like two-domain short-tail receptor 2 (KIR2DS2) is an activating KIR receptor invariably expressed on the cell surface of NK cells and subsets of T cells. The ligand specificity of KIR2DS2 is unknown; it does not bind the HLA-Cw3 molecules recognised by the inhibitory receptor KIR2DL2, despite 99% extracellular amino acid identity (Saulquin et al. 2003). In the presence of DAP12, cross-linking of KIR2DS2 with monoclonal antibody leads to phosphorylation of JNK and ERK and activation of both cytotoxicity and IFN-production.
			REACT_147778 (Reactome)	LAT is palmitoylated and membrane-associated adaptor protein. It rapidly becomes tyrosine-phosphorylated upon receptor engagement. LAT has nine conserved tyrosine residues of which five have been shown to undergo phosphorylation (Y127, Y132, Y171, Y191 and Y226). Src family kinases, SYK and ZAP-70 efficiently phosphorylate LAT on these tyrosine residues (Jiang & Cheng 2007, Paz et al. 2001). Phosphorylation of LAT creates binding sites for the Src homology 2 (SH2) domain proteins PLC-gamma1, GRB2 and GADS, which indirectly bind SOS, VAV, SLP-76 and ITK (Wange 2000).
			REACT_147782 (Reactome)	Killer cell immunoglobulin-like three-domain short-tail receptor 1 (KIR3DS1) is a member of the KIR family expressed on peripheral natural killer (NK) cells and implicated in protection against HIV (Carr et al. 2007, Pascal et al. 2007). The physiological ligand for KIR3DS1 is not clearly determined but it has been suggested to bind HLA-B Bw4-80I on HIV-1-infected target cells (Qi et al. 2006). KIR3DS1 associates with DAP12 and this association enhances its cell surface expression. Crosslinking KIR3DS1 with a monoclonal antibody stimulates NK cell-mediated cytolysis and IFN-gamma production (Carr et al. 2007).
			REACT_147784 (Reactome)	Gads/GRAP2 (GRB2-related adapter protein 2) is member of the GRB2 adaptor family with a central SH2 domain and linker region flanked by amino- and carboxy-terminal SH3 domains. SLP-76 associates constitutively via its central 20-amino acid proline-rich domain with the C-terminal SH3 domain of Gads, which recruits it to LAT following receptor stimulation. Upon LAT phosphorylation, Gads:SLP-76 complex principally binds to phosphorylated LAT tyrosine 191, with a reduced amount of binding to phosphorylated tyrosine 171 and no interaction with phosphorylated tyrosines 132 or 226 (Houtman et al. 2004, Zhu et al. 2003). Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways (Liu et al. 1999). The LAT-Gads-SLP-76 complex creates a platform for the recruitment of multiple signaling molecules, including PLCgamma1, GRB2, NCK, Rho GEFs, VAV and the Tec-family kinases ITK and BTK (Liu et al. 1999 & 2001, Asada et al. 1999, Yablonski et al. 2001).
			REACT_147785 (Reactome)	VAV2 and VAV3 are expressed in human NK cells and play a central role in NK cell-mediated cytotoxicity. They are required for DAP12-mediated signaling; their loss profoundly impairs DAP12-induced cytotoxicity (Billadeau et al. 2000, Cella et al. 2004). Phosphorylated SLP-76 tyrosines Y113 and Y128 provide binding sites for the SH2 domains of VAV. The binding of VAV to these phosphotyrosine residues may link SLP-76 to the Jun amino-terminal kinase (JNK) pathway and the actin cytoskeleton. Y145 has been implicated in the binding of SLP-76 to the Tec family kinase BTK (Kettner et al. 2003). BTK is required for secretion of pro-inflammatory cytokines, phosphorylation of ERK1/2 and PLCgamma and Ca2+ mobilization (Ormsby et al. 2011).
			REACT_147796 (Reactome)	The binding of SYK to DAP12 induces conformational changes that result in SYK activation. Around ten autophosporylated tyrosine residues have been identified in SYK, regulating activity and serving as docking sites for other proteins. Sites include Y131 of interdomain A, Y323, Y348, and Y352 of interdomain B, Y525 and Y526 within the activation loop of the kinase domain and Y630 in the C-terminus (Zhang et al. 2002, Lupher et al. 1998, Furlong et al. 1997). SYK is phosphorylated by Src family kinases and this acts as an initiating trigger by generating a few molecules of activated SYK, which then initiate SYK autophosphorylation (Hillal et al. 1997, Castro et al. 2010)
			REACT_147800 (Reactome)	Myeloid DAP12-associating lectin (MDL)-1, also designated CLEC5A, is a type II transmembrane protein belonging to the C-type lectin superfamily and expressed exclusively in monocytes and macrophages. MDL-1 contains a charged residue in the transmembrane region and this enables it to pair with DAP12 dimers. MDL-1's natural mammalian ligand is unknown, but MDL-1 is a receptor for Dengue virus CLEC5A is critical for dengue-virus-induced lethal disease (Chen et al 2008). Engagement with DAP12 has been shown to regulate osteoclastogenesis and myeloid cell-associated inflammatory responses (Bakker et al. 1999, Aoki et al. 2009, Inui et al 2009, Joyce-Shaikh et al. 2010, Cheung et al. 2011).
			REACT_147801 (Reactome)	Three tyrosine residues at positions 771, 783 and 1254 in PLCgamma1 have been identified as the sites of receptor tyrosine kinase phosphorylation. Of these Y783 and Y1254 are required for PLC-gamma1 activation. In myeloid cells phosphorylation of the tyrosine residues of PLC-gamma1 is mediated by SYK and BTK kinases (Ormsby et al. 2010, Kim et al. 1994, Law et al. 1996, Watanabe et al. 2001).
			REACT_147817 (Reactome)	The phospholipase PLC-gamma is an important mediator of TCR, FCERI and DAP12 signal transduction. PLC-gamma hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) and in-turn promotes the Ca+2 influx and activation of NFAT. Activation of PLC-gamma1 entails the binding of PLC-gamma1 to both LAT and SLP-76 adapter proteins. The amino-terminal SH2 domain of PLC-gamma1 was shown to preferentially bind phosphorylated LAT Y132 with high affinity and no detectable binding to phosphorylated tyrosines 171, 191, and 226. PLC-gamma1 was also shown to bind the adapter protein SLP-76 indirectly through GADS, which is bound to LAT at Y171 and Y191. SH3 domain of PLC-gamma1 associates with the proline-rich region of SLP-76 (Yablonski et al. 2001). PLC-gamma1 associates with Gads/SLP-76 complex before binding to p-Y132 of LAT (Houtman et al. 2005). PLC-gamma1 association with LAT is stabilized by Gads/SLP-76 bound to LAT (Zhu et al.2003). Association of PLC-gamma to LAT and SLP-76 couples it to the kinases (Syk and Tec family kinase) required for tyrosine phosphorylation and activation of PLC-gamma. Mast cells express both PLC-gamma1 and PLC-gamma2 isoforms, which are phosphorylated by BTK/ITK and/or SYK. FCERI-dependent Ca2+ release requires the recruitment of PLC-gamma by SLP-76 and LAT. In mast cells, increased intracellular calcium triggers rapid release of preformed mediators, through a process of vesicle exocytosis, known as degranulation. Recruitment and activation of phospholipase C gamma (PLC-gamma) is involved in DAP12 signal transduction. Phosphorylation of multiple substrates including PLC-gamma1 has been observed in Ly49D/DAP12 triggered NK cells (McVicar et al. 1998). In myeloid cells, PLC-gamma2 is recruited and then phosphorylated upon activation of TREM2 and DAP12 (Peng et al. 2010).
			REACT_147830 (Reactome)	Killer cell immunoglobulin-like two-domain short-tail receptor 1 (KIR2DS1) is one of the activating KIR receptors expressed on the surface of NK cells. It recognizes and binds to ligand HLA-C2:peptide complexes. KIR2DS1 oligomerizes upon interaction with its HLA-Class I ligands. The interaction between the peptide-HLA and KIR2DS1 oligomers leads to activation of the DAP12 signaling cascade. The engagement of KIR2DS1 with HLA-C2 is not sufficient to drive NK cell cytotoxicity or IFN-gamma production (Stewart et al. 2005). Recognition of HLA-C2 by KIR2DS1 is involved in the anti-leukemic activity of alloreactive NK cells and associated with protection against Hodgkin's lymphoma (Cognet et al. 2010). The presence of the HLA-C2 allele HLA-Cw6 in combination with KIR2DS1 is a major risk factor for psoriasis (Ploski et al. 2006).
			REACT_147834 (Reactome)	In myeloid cells BTK is phosphorylated on Y551 upon DAP12 activation in a SYK kinase-dependent manner. Y551 is located in the activation loop of BTK, known to be required for activation and kinase activity. Y223 in the SH3 domain of BTK is autophosphorylated, which may also be involved in BTK activation (Ormsby et al. 2010, Rawlings et al. 1996).
			REACT_147838 (Reactome)	Activated VAV2/3 act as guanine nucleotide exchange factors (GEFs) for RAC-1, catalysing the exchange of bound GDP for GTP.
			REACT_147856 (Reactome)	Activated PI3K phosphorylates phosphatidylinositol (PI) 4-phosphate and PI 4,5-bisphosphate (PIP2) to generate PI 3,4-bisphosphate and PI 3,4,5-triphosphate (PIP3) and these second messengers recruit other signaling proteins containing plecstrin homology (PH) domain. Products of PI3K are involved in the regulation of PLC-gamma 1 and VAV activation. The PH domain of PLC-gamma 1 binds to PIP3 and is targeted to the membrane. PIP3 binds to the PH domain of VAV2/VAV3 and increases it activity and PI3K may also strongly stimulate VAV activity by converting an inhibitory regulator VAV to an activator (Toker & Cantley 1997, Fischer et al. 1998, Falasca et al. 1998).
			REACT_147866 (Reactome)	Killer cell immunoglobulin-like two-domain short-tail receptor 4 (KIR2DS4) is the most prevalent lineage III-activating KIR receptor. It interacts weakly but specifically with HLA-Cw3 and HLA-Cw4 and may also bind to an uncharacterised non-MHC molecule. It can associate with DAP12, activating NK cells.
			REACT_147879 (Reactome)	Phosphoinositide 3-kinases (PI3Ks) are one of the downstream effectors of activated SYK. The p85 alpha regulatory subunit of PI3K has been shown to interact with SYK phospho-tyrosine Y323. In DAP12 signaling SYK acts via the PI3K-dependent pathway to control NK cell-mediated cytotoxicity. SYK-coupled PI3K is rapidly activated and triggers a sequential activation of VAV2/VA3, RAC1, PAK1, MEK and ERK to mediate NK cell-mediated lysis (Jiang et al. 2002, Moon et al. 2005).
			REACT_147897 (Reactome)	TREM proteins (triggering receptors expressed on myeloid cells) are a family of cell surface receptors involved in innate immune responses. They are expressed in myeloid cells and have both positive and negative functions in regulating myeloid cell activation and differentiation. Humans have two members, TREM1 and TREM2. TREM1 is considered an amplifier of the immune response, while TREM2 is believed to be a negative regulator of inflammatory responses (Sharif & Knaap 2008). TREM proteins consist of a single extracellular V-type Ig-like domain, a transmembrane region and a short cytoplasmic tail lacking any signalling motifs (Kelker et al. 2004). Both receptors associate with DAP12 for signalling. The ligand for TREM1 is unknown. TREM1 associates with DAP12 dimer. This interaction is mediated by aspartic acid and adjacent threonine residues in the DAP12 dimer that interface with lysine residues in the TREM1 transmembrane region. TREM1 engagement triggers the production of inflammatory chemokines and cytokines such as IL-8 and myeloperoxidase (MPO) in neutrophils and IL-8, MCP-1, and TNF in monocytes (Tessarz & Cerwenka 2008, Bouchon et al. 2000).
			REACT_23798 (Reactome)	SIRP beta , also named CD172b, is expressed mainly on myeloid cells and has a very short cytoplasmic region of only six amino acids, lacking the signaling motifs for association with phosphatases that are found in the highly related SIRP alpha receptor. Instead, SIRP associates with a dimeric protein DAP12 to transmit activating signals via an ITAM in the cytoplasmic domain of DAP12. A positively charged amino acid in the transmembrane domain of DAP12 associate with a basic amino acid in SIRP beta's transmembrane region.
SIGLEC14/15/16			REACT_147732 (Reactome)
SIRPB1			REACT_23798 (Reactome)
SYK			REACT_147772 (Reactome)
TREM1			REACT_147897 (Reactome)
TREM2			REACT_147773 (Reactome)
TYROBP			REACT_23798 (Reactome)
VAV2/VAV3			REACT_147785 (Reactome)
	p-5Y-LAT GRB2 SOS GADS p-3Y-SLP-76 p-2Y-BTK VAV p-PLCG	Arrow	REACT_147801 (Reactome)
	p-5Y-LAT GRB2 SOS GADS p-3Y-SLP-76 p-2Y-BTK VAV	Arrow	REACT_147702 (Reactome)
	p-5Y-LAT GRB2 SOS1 GADS p-3Y-SLP-76 PLCG VAV p-Y223,Y551-BTK	Arrow	REACT_147834 (Reactome)
p-5Y-LAT GRB2 SOS1 GADS p-3Y-SLP-76 PLCG VAV p-Y223,Y551-BTK			REACT_147801 (Reactome)
p-5Y-LAT GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG VAV BTK PIP3			REACT_147708 (Reactome)
p-5Y-LAT GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG VAV BTK PIP3			REACT_147834 (Reactome)
	p-5Y-LAT PLCG1 GADS p-3Y-SLP-76 BTK p-VAV	Arrow	REACT_147708 (Reactome)
p-5Y-LAT PLCG1 GADS p-3Y-SLP-76 BTK p-VAV			REACT_147838 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1 GADS SLP76 PLCG			REACT_147736 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1 GADS SLP76			REACT_147817 (Reactome)
	p-5Y-LAT p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG	Arrow	REACT_147736 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG			REACT_147785 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1			REACT_147697 (Reactome)
p-5Y-LAT p-SHC1 GRB2 SOS1			REACT_147784 (Reactome)
	p-5Y-LAT-2	Arrow	REACT_147778 (Reactome)
p-5Y-LAT-2			REACT_147717 (Reactome)
	p-PLCG	Arrow	REACT_147702 (Reactome)
p-SHC1 GRB2 SOS			REACT_147717 (Reactome)
p-SYK/p-BTK			REACT_147801 (Reactome)
p21 RAS GDP			REACT_147697 (Reactome)
	p21 RAS GTP	Arrow	REACT_147697 (Reactome)