The insulin receptor （IR） is an important hub in insulin signaling and its activation is tightly regulated. Upon insulin stimulation, IR is activated through autophos- phorylation, and consequently phosphorylates se...The insulin receptor （IR） is an important hub in insulin signaling and its activation is tightly regulated. Upon insulin stimulation, IR is activated through autophos- phorylation, and consequently phosphorylates several insulin receptor substrate （IRS） proteins, including IRS1- 6, Shc and Gab1. Certain adipokines have also been found to activate IR. On the contrary, PTP, Grb and SOCS proteins, which are responsible for the negative regu- lation of IR, are characterized as IR inhibitors. Addi- tionally, many other proteins have been identified as IR substrates and participate in the insulin signaling path- way. To provide a more comprehensive understanding of the signals mediated through IR, we reviewed the upstream and downstream signal molecules of IR, summarized the positive and negative modulators of IR, and discussed the IR substrates and interacting adaptor proteins. We propose that the molecular events associ- ated with IR should be integrated to obtain a better understanding of the insulin signaling pathway and diabetes.展开更多
文摘The insulin receptor （IR） is an important hub in insulin signaling and its activation is tightly regulated. Upon insulin stimulation, IR is activated through autophos- phorylation, and consequently phosphorylates several insulin receptor substrate （IRS） proteins, including IRS1- 6, Shc and Gab1. Certain adipokines have also been found to activate IR. On the contrary, PTP, Grb and SOCS proteins, which are responsible for the negative regu- lation of IR, are characterized as IR inhibitors. Addi- tionally, many other proteins have been identified as IR substrates and participate in the insulin signaling path- way. To provide a more comprehensive understanding of the signals mediated through IR, we reviewed the upstream and downstream signal molecules of IR, summarized the positive and negative modulators of IR, and discussed the IR substrates and interacting adaptor proteins. We propose that the molecular events associ- ated with IR should be integrated to obtain a better understanding of the insulin signaling pathway and diabetes.
