Search results for: JIP_2 Control Peptide
#29570727 
2018/03/23
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miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence.
Theileria annulata is an apicomplexan parasite that infects and transforms bovine macrophages that disseminate throughout the animal causing a leukaemia-like disease called tropical theileriosis. Using deep RNAseq of T. annulata-infected B cells and macrophages we identify a set of microRNAs induced by infection, whose expression diminishes upon loss of the hyper-disseminating phenotype of virulent transformed macrophages. We describe how infection-induced upregulation of miR-126-5p ablates JIP-2 expression to release cytosolic JNK to translocate to the nucleus and trans-activate AP-1-driven transcription of mmp9 to promote tumour dissemination. In non-disseminating attenuated macrophages miR-126-5p levels drop, JIP-2 levels increase, JNK1 is retained in the cytosol leading to decreased c-Jun phosphorylation and dampened AP-1-driven mmp9 transcription. We show that variation in miR-126-5p levels depends on the tyrosine phosphorylation status of AGO2 that is regulated by Grb2-recruitment of PTP1B. In attenuated macrophages Grb2 levels drop resulting in less PTP1B recruitment, greater AGO2 phosphorylation, less miR-126-5p associated with AGO2 and a consequent rise in JIP-2 levels. Changes in miR-126-5p levels therefore, underpin both the virulent hyper-dissemination and the attenuated dissemination of T. annulata-infected macrophages.Malak Haidar, Zineb Rchiad, Hifzur Rahman Ansari, Fathia Ben-Rached, Shahin Tajeri, Perle Latre De Late, Gordon Langsley, Arnab Pain
1256 related Products with: miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence.
200ul100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized 100 UG100ug Lyophilized100 μg100ug Lyophilized5ug
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#23159405 2012/11/15
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Differential regulation of M3/6 (DUSP8) signaling complexes in response to arsenite-induced oxidative stress.
Mitogen-activated protein kinase (MAPK) cascades are involved in the regulation of cellular proliferation, differentiation, survival, apoptosis, as well as in inflammatory responses. Signal intensity and duration have been recognized as crucial parameters determining MAPK signaling output. Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins. The JNK family consists of three genes, giving rise to at least ten different splice variants. Some functional differences between these gene products have been demonstrated, but the underlying molecular mechanisms and the roles of individual splice variants are still incompletely understood. We have investigated the interaction of M3/6 with JNK isoforms, as well as scaffold proteins of the JNK interacting protein (JIP) family, in order to elucidate the contribution of M3/6 to the regulation of distinct JNK signaling modules. M3/6 exhibited stronger binding towards JNK1β and JNK2α isoforms and this was reflected in higher enzymatic activity towards JNK2α2 when compared to JNK1α1 in vitro. After activation of the pathway by exposure of cells to arsenite, the interaction of M3/6 with JNK1α and JNK3 was enhanced, whereas that with JNK1β or JNK2α decreased. The modulation of binding affinities was found to be independent of JNK-mediated M3/6 phosphorylation. Furthermore, arsenite treatment resulted in an inducible recruitment of M3/6 to JNK-interacting protein 3 (JIP3) scaffold complexes, while its interaction with JIP1 or JIP2 was constitutive. The presented data suggest an isoform-specific role for the M3/6 phosphatase and the dynamic targeting of M3/6 towards distinct JNK-containing signaling complexes.Wolf Oehrl, Marina Cotsiki, George Panayotou
2056 related Products with: Differential regulation of M3/6 (DUSP8) signaling complexes in response to arsenite-induced oxidative stress.
100 mg 100 UG 1 G2 Pieces/Box1mg2ug2 Pieces/Box100 100 mg25 14 inhibitors
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Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes.
The sympathetic nervous system regulates the activity and expression of uncoupling protein 1 (UCP1) through the three beta-adrenergic receptor subtypes and their ability to raise intracellular cyclic AMP (cAMP) levels. Unexpectedly, we recently discovered that the cAMP-dependent regulation of multiple genes in brown adipocytes, including Ucp1, occurred through the p38 mitogen-activated protein kinases (MAPK) (W. Cao, K. W. Daniel, J. Robidoux, P. Puigserver, A. V. Medvedev, X. Bai, L. M. Floering, B. M. Spiegelman, and S. Collins, Mol. Cell. Biol. 24:3057-3067, 2004). However, no well-defined pathway linking cAMP accumulation or cAMP-dependent protein kinase (PKA) to p38 MAPK has been described. Therefore, in the present study using both in vivo and in vitro models, we have initiated a retrograde approach to define the required components, beginning with the p38 MAPK isoforms themselves and the MAP kinase kinase(s) that regulates them. Our strategy included ectopic expression of wild-type and mutant kinases as well as targeted inhibition of gene expression using small interfering RNA. The results indicate that the beta-adrenergic receptors and PKA lead to a highly selective activation of the p38alpha isoform of MAPK, which in turn promotes Ucp1 gene transcription. In addition, this specific activation of p38alpha relies solely on the presence of MAP kinase kinase 3, despite the expression in brown fat of MKK3, -4, and -6. Finally, of the three scaffold proteins of the JIP family expressed in brown adipocytes, only JIP2 co-immunoprecipitates p38alpha MAPK and MKK3. Therefore, in the brown adipocyte the recently described scaffold protein JIP2 assembles the required factors MKK3 and p38alpha MAPK linking PKA to the control of thermogenic gene expression.Jacques Robidoux, Wenhong Cao, Hui Quan, Kiefer W Daniel, Fatiha Moukdar, Xu Bai, Lisa M Floering, Sheila Collins