Phospho-IRS1 (Ser318)[Ser323] Antibody - #AF4422

May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).

Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity). Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1. Phosphorylated on tyrosine residues in response to insulin. In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1.

Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2).

Interacts with UBTF and PIK3CA (By similarity). Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity). Interacts with ROCK1 and FER (By similarity). Interacts (via PH domain) with PHIP (By similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7. Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with ALK. Interacts with EIF2AK2/PKR (By similarity). Interacts with GKAP1 (By similarity). Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (By similarity). Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity).