NCAM signaling for neurite out-growth (Homo sapiens)

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1-617104, 8, 99, 111712, 134, 914-16nucleoplasmGolgi lumencytosolATPATPSon of sevenless protein homolog 1Multiple phosphorylated FAK bound to NCAM:pFynPhospho-MSK1Grb2:pFAK bound to NCAM1:pFynT- and L-type VDCCNCAM1NCAM1:GFRalpha-1:GDNFAgrinSRCGrb2:Sos:pFAK bound to NCAM1:pFynGlycosylated NCAM1Polysialic acidp21 RAS:GTPpFyn-Y531RAF activationADPNCAM-1:AgrinNCAM1CREBFGFR1c homodimerNCAM1 complexed with FynADPNCAM1:T- and L-type VDCCGRB2NCAM1 complexed with pFyn-Y420p21 RAS:GDPalpha 2-8 polysialyltransferasesOrthophosphatepFAK (391) bound to NCAM1:pFynGFRalphaADPATPphospho-CREBATPGTPNCAM1 cis-homodimerATPNeurocanNCAM1-Contactin-2Fyn:NCAM1:RPTP-alphaSpectrin heterodimerFADK1ADPReceptor-type tyrosine-protein phosphatase alphaADPAxonin-1MSK1ATPNCAM1:FGFR-1GDPNCAM-1:NeurocanNCAM-1:Major prion proteinMAP kinase cascadeNCAM-1:ATPCollagensFYNPhospho-ERK dimerNCAM-1:Collagen complexGDNF family ligands (GFLs)Polysialylated NCAMNCAM1:NCAM1 trans-homotetramerMajor prion proteinNCAM1:GFRalpha-17


Description

The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons.

NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114681view16:15, 25 January 2021ReactomeTeamReactome version 75
113128view11:19, 2 November 2020ReactomeTeamReactome version 74
112360view15:29, 9 October 2020ReactomeTeamReactome version 73
101261view11:15, 1 November 2018ReactomeTeamreactome version 66
100799view20:43, 31 October 2018ReactomeTeamreactome version 65
100341view19:20, 31 October 2018ReactomeTeamreactome version 64
99886view16:03, 31 October 2018ReactomeTeamreactome version 63
99443view14:37, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99113view12:40, 31 October 2018ReactomeTeamreactome version 62
93875view13:42, 16 August 2017ReactomeTeamreactome version 61
93442view11:23, 9 August 2017ReactomeTeamreactome version 61
88031view13:34, 25 July 2016RyanmillerOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
88028view13:33, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86533view09:20, 11 July 2016ReactomeTeamreactome version 56
83314view10:45, 18 November 2015ReactomeTeamVersion54
81453view12:59, 21 August 2015ReactomeTeamVersion53
76927view08:19, 17 July 2014ReactomeTeamFixed remaining interactions
76632view12:00, 16 July 2014ReactomeTeamFixed remaining interactions
75963view10:02, 11 June 2014ReactomeTeamRe-fixing comment source
75665view10:57, 10 June 2014ReactomeTeamReactome 48 Update
75020view13:53, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74664view08:43, 30 April 2014ReactomeTeamReactome46
42084view21:55, 4 March 2011MaintBotAutomatic update
39892view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Agrin ProteinO00468 (UniProt)
Axonin-1 ProteinQ02246 (UniProt)
CREB ProteinP16220 (UniProt)
Collagens ComplexREACT_18161 (Reactome)
FADK1 ProteinQ05397 (UniProt)
FGFR1c homodimer ComplexREACT_9800 (Reactome)
FYN ProteinP06241 (UniProt)
Fyn:NCAM1:RPTP-

alpha

ComplexREACT_18571 (Reactome)
GDNF family ligands

(GFLs)

ProteinREACT_20000 (Reactome)
GDP Metabolite17552 (ChEBI)
GFRalpha ProteinREACT_19467 (Reactome)
GRB2 ProteinP62993-1 (UniProt)
GTP Metabolite15996 (ChEBI)
Glycosylated NCAM1 ProteinP13591 (UniProt)
Grb2:Sos:pFAK

bound to NCAM1: pFyn

ComplexREACT_18839 (Reactome)
Grb2:pFAK bound to

NCAM1:pFyn

ComplexREACT_18783 (Reactome)
MAP kinase

cascade

PathwayREACT_634 (Reactome) 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.
MSK1 ProteinO75582 (UniProt)
Major prion protein ProteinP04156 (UniProt)
Multiple

phosphorylated FAK bound to NCAM:pFyn

ComplexREACT_18768 (Reactome)
NCAM-1:ATP ComplexREACT_18582 (Reactome)
NCAM-1:Agrin ComplexREACT_19071 (Reactome)
NCAM-1:Collagen

complex

ComplexREACT_18833 (Reactome)
NCAM-1:Major prion

protein

ComplexREACT_18842 (Reactome)
NCAM-1:Neurocan ComplexREACT_18891 (Reactome)
NCAM1 ProteinP13591 (UniProt)
NCAM1 cis-

homodimer

ComplexREACT_19070 (Reactome)
NCAM1 complexed

with Fyn

ComplexREACT_18556 (Reactome)
NCAM1 complexed

with pFyn-Y420

ComplexREACT_18470 (Reactome)
NCAM1-Contactin-2 ComplexREACT_19032 (Reactome)
NCAM1:FGFR-1 ComplexREACT_18900 (Reactome)
NCAM1:GFRalpha-1 ComplexREACT_18445 (Reactome)
NCAM1:GFRalpha-1:

GDNF

ComplexREACT_18598 (Reactome)
NCAM1:NCAM1

trans-homotetramer

ComplexREACT_18931 (Reactome)
NCAM1:T- and L-

type VDCC

ComplexREACT_21777 (Reactome)
Neurocan ProteinO14594 (UniProt)
Orthophosphate Metabolite18367 (ChEBI)
Phospho-ERK dimer UnknownREACT_12827 (Reactome)
Phospho-MSK1 ProteinO75582 (UniProt)
Polysialic acid UnknownREACT_18892 (Reactome)
Polysialylated NCAM ComplexREACT_18914 (Reactome)
RAF activation PathwayREACT_2077 (Reactome) Phosphorylated RAF is activated by Ras binding and stabilised in its active form by transient disassociation and reassociation of 14-3-3, as well as further phosphorylation.
Receptor-type

tyrosine-protein phosphatase alpha

ProteinP18433 (UniProt)
SRC ProteinP12931-1 (UniProt)
Son of sevenless

protein homolog 1

ProteinQ07889 (UniProt)
Spectrin heterodimer ComplexREACT_19000 (Reactome) Spectrin is a protein found at the intracellular surface of the plasma membrane in many cell types. In association with other proteins particularly protein 4.1 and ankyrin it forms hexagonal or pentagonal structures that act as a plasma membrane scaffold for other membrane structures and as an attachment point for cytoskeletal proteins such as actin. The erythrocyte forms of spectrin are the best studied (and not exclusievely expressed in erthrocytes).
T- and L-type VDCC ProteinREACT_21538 (Reactome)
alpha 2-8

polysialyltransferases

UnknownREACT_18945 (Reactome)
p21 RAS:GDP ComplexREACT_2657 (Reactome)
p21 RAS:GTP ComplexREACT_4782 (Reactome)
pFAK (391) bound to

NCAM1:pFyn

ComplexREACT_18498 (Reactome)
pFyn-Y531 ProteinP06241 (UniProt)
phospho-CREB ProteinP16220 (UniProt)

Annotated Interactions

No annotated interactions

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