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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology

2009

Series

Open Access Articles

Articles 1 - 2 of 2

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Signal Transduction Cross Talk Mediated By Jun N-Terminal Kinase-Interacting Protein And Insulin Receptor Substrate Scaffold Protein Complexes, Claire L. Standen, Norman J. Kennedy, Richard A. Flavell, Roger J. Davis Jul 2009

Signal Transduction Cross Talk Mediated By Jun N-Terminal Kinase-Interacting Protein And Insulin Receptor Substrate Scaffold Protein Complexes, Claire L. Standen, Norman J. Kennedy, Richard A. Flavell, Roger J. Davis

Open Access Articles

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 ...


Mcl-1 Integrates The Opposing Actions Of Signaling Pathways That Mediate Survival And Apoptosis, Caroline Morel, Scott M. Carlson, Forest M. White, Roger J. Davis May 2009

Mcl-1 Integrates The Opposing Actions Of Signaling Pathways That Mediate Survival And Apoptosis, Caroline Morel, Scott M. Carlson, Forest M. White, Roger J. Davis

Open Access Articles

Mcl-1 is a member of the Bcl2-related protein family that is a critical mediator of cell survival. Exposure of cells to stress causes inhibition of Mcl-1 mRNA translation and rapid destruction of Mcl-1 protein by proteasomal degradation mediated by a phosphodegron created by glycogen synthase kinase 3 (GSK3) phosphorylation of Mcl-1. Here we demonstrate that prior phosphorylation of Mcl-1 by the c-Jun N-terminal protein kinase (JNK) is essential for Mcl-1 phosphorylation by GSK3. Stress-induced Mcl-1 degradation therefore requires the coordinated activity of JNK and GSK3. Together, these data establish that Mcl-1 functions as a site of signal integration between the ...