Figure 1.

Insulin signaling. Insulin binds to IR leading to autophosphorylation of IR; thus, IR could recruit diverse substrates. The two main responses of insulin signaling are mitogenic signaling (begin with SHC and GRB2 through the ERK1/2 pathway) and metabolic signaling (begin with IRS through the AKT pathway and SH2B2/APS through CRK/TC10 pathway). The regulation of insulin signaling could be characterized by negative feedback mechanisms, such as stabilization and recruitment of GRB10 to the IR; activation of lipid phosphatases (PTEN, SHIP1, and SHIP2) that dephosphorylate PIP3; and activation of several stress kinases (IKK, JNK, S6K, and mTORC1) to phosphorylate and inhibit IR and IRS. Green circles and arrows represent activating events; red circles and lines represent inhibitory events. pY: phosphorylated tyrosine residue.