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Articles 1 - 7 of 7

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

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 ...


Inflammation Mediated By Jnk In Myeloid Cells Promotes The Development Of Hepatitis And Hepatocellular Carcinoma, Myoung Souk Han, Tamera Barrett, Michael A. Brehm, Roger J. Davis Apr 2016

Inflammation Mediated By Jnk In Myeloid Cells Promotes The Development Of Hepatitis And Hepatocellular Carcinoma, Myoung Souk Han, Tamera Barrett, Michael A. Brehm, Roger J. Davis

Davis Lab Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is required for the development of hepatitis and hepatocellular carcinoma. A role for JNK in liver parenchymal cells has been proposed, but more recent studies have implicated non-parenchymal liver cells as the relevant site of JNK signaling. Here, we tested the hypothesis that myeloid cells mediate this function of JNK. We show that mice with myeloid cell-specific JNK deficiency exhibit reduced hepatic inflammation and suppression of both hepatitis and hepatocellular carcinoma. These data identify myeloid cells as a site of pro-inflammatory signaling by JNK that can promote liver pathology. Targeting myeloid cells with ...


Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis Feb 2016

Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis

Davis Lab Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is implicated in the response to metabolic stress. Indeed, it is established that the ubiquitously expressed JNK1 and JNK2 isoforms regulate energy expenditure and insulin resistance. However, the role of the neuron-specific isoform JNK3 is unclear. Here we demonstrate that JNK3 deficiency causes hyperphagia selectively in high fat diet (HFD)-fed mice. JNK3 deficiency in neurons that express the leptin receptor LEPRb was sufficient to cause HFD-dependent hyperphagia. Studies of sub-groups of leptin-responsive neurons demonstrated that JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic response. These ...


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.


Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger Apr 2008

Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger

Davis Lab Publications

Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss ...


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 ...