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Figure 3 | Molecular Medicine

Figure 3

From: Insulin Signaling and the Regulation of Glucose Transport

Figure 3

A model for diverse signaling pathways in insulin action. Two signaling pathways are required for the translocation of the glucose transporter Glut4 by insulin in fat and muscle cells. Tyrosine phosphorylation of the IRS proteins after insulin stimulation leads to an interaction with and subsequent activation of PI 3-kinase, producing PIP3, which in turn activates and localizes protein kinases such as PDK1. These kinases then initiate a cascade of phosphorylation events, resulting in the activation of Akt and/or atypical PKC. AS160, a substrate of Akt, plays an as yet undefined role in Glut4 translocation through its Rab-GTPase activating domain. A separate pool of the insulin receptor can also phosphorylate the substrates Cbl and APS. Cbl interacts with CAP, which can bind to the lipid raft protein flotillin. This interaction recruits phosphorylated Cbl into the lipid raft, resulting in the recruitment of CrkII. CrkII binds constitutively to the exchange factor C3G, which can catalyze the exchange of GDP for GTP on the lipid-raft-associated protein TC10. Upon its activation, TC10 interacts with a number of potential effector molecules, including CIP4, Exo70, and Par6/Par3/PKCλ, in a GTP-dependent manner.

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