Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kα pathway

摘要: As insulin-like growth factor-1 (IGF-1) is present in the alpha granules of platelets and its receptor expressed on platelet surface, it may contribute to amplification responses pathogenesis cardiovascular disease. The functional signaling pathways that are involved IGF-1 modulation function, however, presently unknown. Here, I report stimulation results dose-dependent phosphorylation IGF range 1 100 nM. Phosphorylation rapid sustained, with maximal reached within minute. Furthermore, stimulates tyrosine insulin substrate-1 (IRS-1) IRS-2 their association p85 subunit phosphoinositide-3 kinase (PI3K). IGF-1-stimulated IRS-1 subsequent binding transient precedes protein B (PKB) Ser473. PAR-1-mediated aggregation potentiated by this potentiation, together PKB phosphorylation, abolished PI3Kalpha inhibitors PI-103 PIK-75. Importantly, inhibitor NVP-AEW541 neutralization antibody alphaIR3 inhibit SFLLRN-stimulated aggregation, implicating autocrine regulation function. These demonstrate activates receptor/IRS/PI3K/PKB pathway, essential for potentiatory effect responses.