Signal transduction cross talk mediated by Jun N-terminal kinase-interacting protein and insulin receptor substrate scaffold protein complexes
Program in Molecular Medicine
1-Phosphatidylinositol 3-Kinase; Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Base Sequence; Cell Line, Tumor; DNA Mutational Analysis; Dietary Fats; Enzyme Activation; Glucose; Humans; Insulin; Insulin Receptor Substrate Proteins; JNK Mitogen-Activated Protein Kinases; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Pancreas; Point Mutation; Proteome; Signal Transduction
Life Sciences | Medicine and Health Sciences
Scaffold proteins have been established as important mediators of signal transduction specificity. The insulin receptor substrate (IRS) proteins represent a critical group of scaffold proteins that are required for signal transduction by the insulin receptor, including the activation of phosphatidylinositol 3 kinase. The c-Jun NH(2)-terminal kinase (JNK)-interacting proteins (JIPs) represent a different group of scaffold molecules that are implicated in the regulation of the JNK. These two signaling pathways are functionally linked because JNK can phosphorylate IRS1 on the negative regulatory site Ser-307. Here we demonstrate the physical association of these signaling pathways using a proteomic approach that identified insulin-regulated complexes of JIPs together with IRS scaffold proteins. Studies using mice with JIP scaffold protein defects confirm that the JIP1 and JIP2 proteins are required for normal glucose homeostasis. Together, these observations demonstrate that JIP proteins can influence insulin-stimulated signal transduction mediated by IRS proteins.
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Citation: Mol Cell Biol. 2009 Sep;29(17):4831-40. Epub 2009 Jun 29. Link to article on publisher's site
Standen, Claire L.; Kennedy, Norman J.; Flavell, Richard A.; and Davis, Roger J., "Signal transduction cross talk mediated by Jun N-terminal kinase-interacting protein and insulin receptor substrate scaffold protein complexes" (2009). Open Access Articles. Paper 2178.