Signaling by insulin receptor (Homo sapiens)
From WikiPathways
Description
Signal transduction by the insulin receptor is not limited to its activation at the cell surface. The activated ligand-receptor complex initially at the cell surface, is internalised into endosomes itself a process which is dependent on tyrosine autophosphorylation. Endocytosis of activated receptors has the dual effect of concentrating receptors within endosomes and allows the insulin receptor tyrosine kinase to phosphorylate substrates that are spatially distinct from those accessible at the plasma membrane. Acidification of the endosomal lumen, due to the presence of proton pumps, results in dissociation of insulin from its receptor. (The endosome constitutes the major site of insulin degradation). This loss of the ligand-receptor complex attenuates any further insulin-driven receptor re-phosphorylation events and leads to receptor dephosphorylation by extra-lumenal endosomally-associated protein tyrosine phosphatases (PTPs). The identity of these PTPs is not clearly established yet. A discussion of candidates will be added in the near future.</div>
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
3',5'-Cyclic AMP | Metabolite | 17489 (ChEBI) | |
40S small ribosomal
protein 6 | Protein | P62753 (UniProt) | |
4E-BP1-P | Protein | Q13541 (UniProt) | |
ADP | Metabolite | 16761 (ChEBI) | |
AMP | Metabolite | 16027 (ChEBI) | |
ATP | Metabolite | 15422 (ChEBI) | |
Activated ERK1 | Protein | P27361 (UniProt) | |
Activated ERK2 | Protein | P28482 (UniProt) | |
Activated PI3K | Unknown | REACT_9165 (Reactome) | |
Activated RAF1
complex | Complex | REACT_4906 (Reactome) | |
Activated RAF1
complex:MEK | Complex | REACT_3953 (Reactome) | |
Activated RAF1
complex:MEK1 | Complex | REACT_4256 (Reactome) | |
Activated RAF1
complex:MEK2 | Complex | REACT_4223 (Reactome) | |
Activated mTORC1 | Complex | REACT_7770 (Reactome) | |
Crk:IRS-P | Complex | REACT_4822 (Reactome) | |
Crk:SOS:IRS-P | Complex | REACT_2957 (Reactome) | |
ERK1 | Protein | P27361 (UniProt) | |
ERK2 | Protein | P28482 (UniProt) | |
GDP | Metabolite | 17552 (ChEBI) | |
GRB10 | Protein | Q13322 (UniProt) | |
GRB10:INSR | Complex | REACT_5054 (Reactome) | |
GRB2:IRS-P | Complex | REACT_5160 (Reactome) | |
GRB2:SOS1 | Complex | REACT_4435 (Reactome) | |
GRB2:SOS:IRS-P | Complex | REACT_3414 (Reactome) | |
GRB2:SOS:Phospho-
SHC | Complex | REACT_2380 (Reactome) | |
GRB2:phospho-SHC | Complex | REACT_2584 (Reactome) | |
GTP | Metabolite | 15996 (ChEBI) | |
H+ | Metabolite | 15378 (ChEBI) | |
H2O | Metabolite | 15377 (ChEBI) | |
IDA | Unknown | REACT_2385 (Reactome) | |
IRS | Protein | REACT_2507 (Reactome) | The proteins mentioned here are examples of IRS family members acting as indicated for IRS. More family members are to be confirmed and added in the future. |
IRS:activated insulin
receptor | Complex | REACT_3393 (Reactome) | |
Insulin receptor | Complex | REACT_5691 (Reactome) | The human insulin receptor is expressed as two isoforms that are generated by alternate splicing of its mRNA; the B isoform has 12 additional amino acids (718-729) encoded by exon 11 of the gene. |
MEK | Protein | REACT_2275 (Reactome) | |
MEK1 | Protein | REACT_2607 (Reactome) | |
MEK1:ERK-1 | Complex | REACT_5539 (Reactome) | |
MEK2:ERK-2 | Complex | REACT_5435 (Reactome) | |
Orthophosphate | Metabolite | 18367 (ChEBI) | |
PDK1 | Protein | O15530 (UniProt) | |
PI3K | Complex | REACT_4240 (Reactome) | |
PIP3:AKT2 complex | Complex | REACT_4871 (Reactome) | |
PIP3:PDK1 complex | Complex | REACT_5409 (Reactome) | |
PIP3:Phosphorylated
PKB complex | Complex | REACT_3373 (Reactome) | |
PKB regulator | Protein | REACT_5778 (Reactome) | |
PKB:PKB Regulator | Complex | REACT_4747 (Reactome) | |
Phosphatidyl-
myo-inositol 4,5- bisphosphate | Unknown | 18348 (ChEBI) | |
Phosphatidylinositol-
3,4,5-trisphosphate | Unknown | 16618 (ChEBI) | |
Phospho-SHC | Protein | REACT_12146 (Reactome) | |
Phosphodiesterase
3B | Protein | Q13370 (UniProt) | Can hydrolyze both cAMP and cGMP |
Phosphorylated
PDE3B | Protein | Q13370 (UniProt) | |
Phosphorylated
Raptor | Protein | Q8N122-1 (UniProt) | |
Phosphorylated 40S
small ribosomal protein 6 | Protein | P62753 (UniProt) | |
RAF activation | Pathway | REACT_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. |
Raptor | Protein | REACT_7195 (Reactome) | |
Rheb:GDP | Complex | REACT_7464 (Reactome) | |
Rheb:GTP | Complex | REACT_7765 (Reactome) | |
S6K1 | Protein | P23443 (UniProt) | |
S6K1-P | Protein | P23443 (UniProt) | |
SHC1 | Protein | P29353 (UniProt) | |
SHC:activated insulin
receptor | Complex | REACT_3791 (Reactome) | |
TSC1:Inhibited TSC2-
1-P | Complex | REACT_7650 (Reactome) | |
TSC1:TSC2 | Complex | REACT_7850 (Reactome) | |
TSC2-1 | Protein | P49815-1 (UniProt) | |
V-ATPase | Complex | REACT_24332 (Reactome) | |
activated insulin
receptor | Complex | REACT_3057 (Reactome) | |
activated insulin
receptor | Complex | REACT_4836 (Reactome) | |
eEF2K | Protein | O00418 (UniProt) | |
eEF2K-P | Protein | O00418 (UniProt) | |
eIF4B | Protein | P23588 (UniProt) | |
eIF4B-P | Protein | P23588 (UniProt) | |
eIF4E | Protein | P06730 (UniProt) | |
eIF4E:4E-BP | Complex | REACT_3978 (Reactome) | |
eIF4E:4E-BP1-P | Complex | REACT_7838 (Reactome) | |
eIF4G | Protein | Q04637 (UniProt) | |
eIF4G-P | Protein | Q04637 (UniProt) | |
insulin | Complex | REACT_3655 (Reactome) | |
insulin | Complex | REACT_5828 (Reactome) | |
insulin receptor | Complex | REACT_3854 (Reactome) | |
insulin:insulin
receptor | Complex | REACT_3518 (Reactome) | |
mLst8 | Protein | Q9BVC4 (UniProt) | |
mTOR | Protein | P42345 (UniProt) | |
p(Y317)-SHC | Protein | P29353 (UniProt) | |
p-(Ser-93, 1130,
Thr-1462)-TSC2-1 | Protein | P49815-1 (UniProt) | |
p21 RAS:GDP | Complex | REACT_2657 (Reactome) | |
p21 RAS:GTP | Complex | REACT_4782 (Reactome) | |
phospho-Cdc2 (Thr
161) | Protein | P06493 (UniProt) | |
phospho-ERK-1
dimer | Complex | REACT_3152 (Reactome) | |
phospho-ERK-1
dimer | Complex | REACT_3932 (Reactome) | |
phospho-ERK-1:
MEK1 | Complex | REACT_2796 (Reactome) | |
phospho-ERK-2
dimer | Complex | REACT_3688 (Reactome) | |
phospho-ERK-2
dimer | Complex | REACT_5046 (Reactome) | |
phospho-ERK-2:
MEK2 | Complex | REACT_3199 (Reactome) | |
phospho-IRS | Protein | REACT_4422 (Reactome) | |
phospho-IRS-
1/2 | Protein | REACT_4523 (Reactome) | |
phospho-IRS:
activated insulin receptor | Complex | REACT_4013 (Reactome) | |
phospho-IRS:PI3K | Complex | REACT_3175 (Reactome) | |
phospho-MEK1 | Protein | Q02750 (UniProt) | |
phospho-MEK2 | Protein | P36507 (UniProt) | |
phospho-SHC:
activated insulin receptor | Complex | REACT_4738 (Reactome) | |
phospho-SOS | Protein | Q07889 (UniProt) | |
phospho-insulin
receptor | Complex | REACT_3809 (Reactome) | |
phospho_MEK1 | Protein | REACT_3339 (Reactome) | |
protein tyrosine
phosphatase | Unknown | REACT_3980 (Reactome) |