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Developmental Biology

University of Massachusetts Medical School

JNK

Articles 1 - 5 of 5

Full-Text Articles in Molecular Biology

Jip1-Mediated Jnk Activation Negatively Regulates Synaptic Plasticity And Spatial Memory, Caroline Morel, Tessi Sherrin, Norman J. Kennedy, Kelly H. Forest, Seda Barutcu, Michael Robles, Ezekiel Carpenter-Hyland, Naghum Alfulaij, Claire L. Standen, Robert A. Nichols, Morris Benveniste, Roger J. Davis, Cedomir Todorovic Apr 2018

Jip1-Mediated Jnk Activation Negatively Regulates Synaptic Plasticity And Spatial Memory, Caroline Morel, Tessi Sherrin, Norman J. Kennedy, Kelly H. Forest, Seda Barutcu, Michael Robles, Ezekiel Carpenter-Hyland, Naghum Alfulaij, Claire L. Standen, Robert A. Nichols, Morris Benveniste, Roger J. Davis, Cedomir Todorovic

University of Massachusetts Medical School Faculty Publications

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis Aug 2016

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab Publications

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


The Role Of Jnk In The Development Of Hepatocellular Carcinoma, Madhumita Das, David S. Garlick, Dale Greiner, Roger J. Davis Mar 2011

The Role Of Jnk In The Development Of Hepatocellular Carcinoma, Madhumita Das, David S. Garlick, Dale Greiner, Roger J. Davis

Davis Lab Publications

The cJun NH(2)-terminal kinase (JNK) signal transduction pathway has been implicated in the growth of carcinogen-induced hepatocellular carcinoma. However, the mechanism that accounts for JNK-regulated tumor growth is unclear. Here we demonstrate that compound deficiency of the two ubiquitously expressed JNK isoforms (JNK1 and JNK2) in hepatocytes does not prevent hepatocellular carcinoma development. Indeed, JNK deficiency in hepatocytes increased the tumor burden. In contrast, compound JNK deficiency in hepatocytes and nonparenchymal cells reduced both hepatic inflammation and tumorigenesis. These data indicate that JNK plays a dual role in the development of hepatocellular carcinoma. JNK promotes an inflammatory hepatic ...


Jnk Regulates Foxo-Dependent Autophagy In Neurons, Ping Xu, Madhumita Das, Judith Reilly, Roger J. Davis Feb 2011

Jnk Regulates Foxo-Dependent Autophagy In Neurons, Ping Xu, Madhumita Das, Judith Reilly, Roger J. Davis

Davis Lab Publications

The cJun N-terminal kinase (JNK) signal transduction pathway is implicated in the regulation of neuronal function. JNK is encoded by three genes that play partially redundant roles. Here we report the creation of mice with targeted ablation of all three Jnk genes in neurons. Compound JNK-deficient neurons are dependent on autophagy for survival. This autophagic response is caused by FoxO-induced expression of Bnip3 that displaces the autophagic effector Beclin-1 from inactive Bcl-XL complexes. These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons.


Requirement Of Jip Scaffold Proteins For Nmda-Mediated Signal Transduction, Norman J. Kennedy, Gilles Martin, Anka G. Ehrhardt, Julie Cavanagh-Kyros, Chia-Yi Kuan, Pasko Rakic, Richard A. Flavell, Steven N. Treistman, Roger J. Davis Sep 2007

Requirement Of Jip Scaffold Proteins For Nmda-Mediated Signal Transduction, Norman J. Kennedy, Gilles Martin, Anka G. Ehrhardt, Julie Cavanagh-Kyros, Chia-Yi Kuan, Pasko Rakic, Richard A. Flavell, Steven N. Treistman, Roger J. Davis

Davis Lab Publications

JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways. To test the physiological role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. These mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evoked current amplitude, cytoplasmic Ca(++), and gene expression. The decreased NMDA receptor activity in JIP-deficient neurons is associated with reduced tyrosine phosphorylation of NR2 subunits of the NMDA receptor. JIP complexes interact with the SH2 domain of cFyn and may therefore promote tyrosine phosphorylation and activity of ...