Insulin receptor signaling through non-tyrosine kinase pathways: evidence from anti-receptor antibodies and insulin receptor mutants.

Although there is general agreement that insulin receptor tyrosine kinase activity mediates many of the actions of insulin, two types of studies suggest that non-tyrosine kinase dependent pathways may also exist. First, both monoclonal and polyclonal antibodies to the receptor have been shown to mediate many of insulin's actions with little or no stimulation of receptor kinase. Second, insulin receptor mutants, with reduced or no tyrosine kinase activity, have been shown to mediate several actions of insulin. Non-tyrosine kinase pathways that could signal insulin effects through the insulin receptor include non-covalent activation of G proteins, phospholipase Cs, or docking proteins such as IRS-1. Further studies on the chemical structures of phospholipids and their hydrolysis products involved in insulin action will be required to sort out the underlying mechanisms of insulin action via non-tyrosine kinase dependent pathways.