Phosphatidylinositol 3-kinase and protein kinase D1 specifically cooperate to negatively regulate the insulin-like growth factor signaling pathway

► PI 3-kinase and PKD1cooperate to inhibit the IGF-I pathway at the level of IRS-1. ► PKD1 is activated independently of PI 3-kinase. ► PKD1 interacts with IRS-1 in response to EGF and FGF. ► PI 3-kinase, but not PKD1, induces the ser-307 phosphorylation of IRS-1. ► IRS-1 Ser-307 phosphorylation is not sufficient per se to inhibit the IGF signaling.