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University of Massachusetts Medical School

Cellular and Molecular Physiology

2009

Articles 1 - 3 of 3

Full-Text Articles in Life Sciences

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 ...


Nuclear Localization Of P38 Mapk In Response To Dna Damage, C. David Wood, Tina Thornton, Guadalupe Sabio, Roger J. Davis, Mercedes Rincon Jun 2009

Nuclear Localization Of P38 Mapk In Response To Dna Damage, C. David Wood, Tina Thornton, Guadalupe Sabio, Roger J. Davis, Mercedes Rincon

Davis Lab Publications

p38 MAP kinase (MAPK) is activated in response to environmental stress, cytokines and DNA damage, and mediates death, cell differentiation and cell cycle checkpoints. The intracellular localization of p38 MAPK upon activation remains unclear, and may depend on the stimulus. We show here that activation of p38 MAPK by stimuli that induce DNA double strand breaks (DSBs), but not other stimuli, leads to its nuclear translocation. In addition, naturally occurring DSBs generated through V(D)J recombination in immature thymocytes also promote nuclear accumulation of p38 MAPK. Nuclear translocation of p38 MAPK does not require its catalytic activity, but is ...


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 ...