insulin receptor substrate 4 (IRS-4, 160 kD phosphotyrosine protein, PY160, IRS4)
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Function
- acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R & FGFR1, & a complex network of intracellular signaling molecules containing SH2 domains
- involved in the IGF1R mitogenic signaling pathway
- promotes the AKT1 signaling pathway & BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis
- interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity
- may be involved in nonreceptor tyrosine kinase signaling in myoblasts
- plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation
- may play a role in the signal transduction in response to insulin & to a lesser extent in response to IL4 & GH on mitogenesis.
- plays a role in growth, reproduction & glucose homeostasis
- may act as negative regulators of the IGFI signaling pathway by suppressing the function of IRS1 & IRS2
- interacts with SOCS6 in response to stimulatiom with either insulin or IGF1 (putative)
- interacts with CRK & CRKL
- interaction with CRK is stronger than with CRKL
- interacts with CRK via the phosphorylated YXXM motifs
- interacts with GRB2 & PIK3R1
- interacts with PLC-gamma, SHC1, PTK6, PPP4C & NISCH
- phosphorylated on Tyr in response to both insulin & IGF1 signaling
- phosphorylated on Tyr-921 in response to FGF2 signaling
- phosphorylation of Tyr-921 is required for GRB2, phospholipase C-gamma & phosphatidylinositol 3-kinase interaction
Structure
- contains 1 IRS-type PTB domain
- contains 1 PH domain
Compartment
cell membrane, cytoplasmic side
Expression
- expressed in myoblasts
- expressed in liver & hepatocellular carcinoma
- down-regulated by PPP4C (phosphatase-dependent)