MAPK11

..Here we characterize a new MAP kinase, p38beta. p38beta is a 372-amino acid protein most closely related to p38...

..MSK1 is activated in vitro by MAPK2/ERK2 or SAPK2/p38...

..Moreover, we show that p38alpha/p38beta and phosphoinositide 3-kinase are crucial to Tat-induced IL-10 production...

..It is conceivable that both modes of action play an important role in controlling the proteolytic phenotype of fibroblasts, e.g. in wound repair and tumor invasion...

..Thus, these newly described pathways act concomitantly with the activation of c-Jun by JNK/MAPKs, thereby contributing to the complexity of AP1-driven gene transcription regulation...

..In this study, we found that stress-activated protein kinase (SAPK)1/c-Jun N-terminal kinase 1 and SAPK2/p38 are involved in the control of MCP-1-induced MonoMac6 cell migration...

..belongs to a class of pyridinyl imidazoles that inhibits the stress-activated protein (SAP) kinases SAPK2a/p38 and SAPK2b/p38 beta 2 but not other mitogen-activated protein kinase family members...

..gene transcription were both prevented by SB 203580, a specific inhibitor of stress-activated protein kinase 2 (SAPK2, also termed p38 mitogen-activated protein kinase, reactivating kinase, CSBP, and Mxi2) but not by several other ..

....

..While p42/p44 MAPK (mitogen-activated protein kinase), SAPK2 (stress-activated protein kinase 2)/p38 and PKC (protein kinase C) were all activated by PMA in HeLa cells, the ..

Sodium arsenite and osmotic shock both stimulated stress-activated protein kinase-2 (SAPK2, also termed RK, p38, CSBP and Mxi2) and its downstream target mitogen-activated protein kinase (MAP kinase)-activated protein kinase-2 (MAPKAP-K2)..

..To investigate the effects of radiation on the endothelial cytoskeleton and endothelial monolayer permeability and to evaluate associated signaling pathways, which could reveal potential mechanisms of known vascular effects of radiation...

..SKK4 activated SAPK1/JNK in vitro, but not SAPK2a/p38, SAPK2b/p38beta, SAPK3/ERK6 or SAPK4. It appears to be the mammalian homologue of HEP, an activator of SAPK1/JNK in Drosophila...

..kinases SAPK1gamma (also called JNK1), SAPK2a (also called p38, RK, CSBPs, Mpk2 and Mxi2), SAPK2b (also called p38beta), SAPK3 (also called ERK6 and p38gamma) and SAPK4 phosphorylate tau at many serine/threonine-prolines, as ..

p38alpha and p38beta MAPKs (mitogen-activated protein kinases) share about 80% of their protein sequence identity, but have quite different biological functions...

..On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading...

..Their current and possible future application as therapeutics in cancer, restenosis, angiogenesis, and osteoporosis is briefly discussed...

..Both vasoconstrictors activated p38alpha and/or p38beta but not p38gamma or p38delta, leading to increased HSP kinase activity...

..Overexpression of p38beta2, but not of p38alpha, significantly decreased PDGF-BB-induced MMP-1 promoter activity, although PDGF-BB activated ..

..PDGF)-induced DNA synthesis, extracellular-regulated kinase 1/2 (ERK1/2), p38/stress-activated protein kinase 2 (SAPK2), RhoA and Rac1 activation...

..This interaction activates, in the cancer cells, the MAPK SAPK2/p38, which leads to their transendothelial migration (Laferrière et al., J Biol Chem 2001; 276: 33762)...

..It is not blocked by SB 203580, which inhibits SAPK2a/p38alpha and SAPK2b/p38beta but not SAPK3/p38gamma, or by the ERK pathway inhibitor PD 184352...

..phosphorylation is prevented by SB 203580, an inhibitor of SAPK2a (stress-activated protein kinase 2a)/p38a and SAPK2b/p38b, and does not occur in embryonic fibroblasts generated from SAPK2a/p38a-deficient mice...

....

..signal-regulated kinase (ERK) cascade, the c-Jun N-terminal kinase (JNK or SAPK1) cascade, and the p38-MAPK (SAPK2-5) cascade...

..In conclusion, our study demonstrates that the endogenous and exogenous PPAR-alpha ligands reduce the degree of macrophage inflammation caused by LPS/IFN-gamma stimulation...

..This phosphorylation is dependent on the kinase p38/SAPK2 and correlates with the activation of MAPKAP kinase 2 (MK2)...

..stresses, interleukin-1 (IL-1) and tumour necrosis factor (TNF) in a similar manner to SAPK1 (also termed JNK) and SAPK2 (also termed p38, RK, CSBP and Mxi2)...

..Transcripts encoding stress-activated protein kinase-3 are widely expressed, with high levels in skeletal muscle...

..The four mammalian isoforms (p38alpha, p38beta, p38gamma, and p38delta) are coexpressed and coactivated in the same cells...

..A concomitant impairment in stress-activated protein kinase (SAPK2/p38) phosphorylation suggests that ATL inhibition of VEGF-stimulated actin polymerization involves the SAPK2/p38 ..

..stress-activated protein kinase 1/ Jun N-terminal kinase (SAPK1), and stress-activated protein kinase 2/ p38 (SAPK2), were measured in gill epithelium of the euryhaline teleost Fundulus heteroclitus exposed for 1 h to 4 weeks to ..

..The selective inhibitor of stress-activated protein kinase 2 (SAPK2), SB 203580, inhibited completely anisomycin-induced glucose uptake but only partly suppressed uptake stimulated ..

..accompanied by a strong activation of p70 S6 kinase and the mitogen-activated protein kinase (MAPK) family member SAPK2/p38, without significant activation of p42 MAPK and only slight activation of SAPK1/JNK and protein kinase Balpha...

..Initial studies confirmed that PGE2 induces egr-1 mRNA expression and protein synthesis by restricted SAPK2/p38 MAPK-dependent activating transcription factor-2 (ATF-2) dimer transactivation of the egr-1 promoter as judged ..

..Our results indicate that the p38-MAPK/MSK1/MSK2 and CREB signalling pathway may play a role in the pathogenesis of psoriasis...

..Raf is a proto-oncogene that is activated in response to growth factors or phorbol esters, and is thought to activate MAP kinase kinase-1 (MKK1) and hence the classical MAP kinase (MAPK) cascade...

..treatment with the MAP kinase (MAPK) inhibitor SB203580, which specifically blocks the stress inducible p38/SAPK2 pathway, did not alter egr-1 induction...

..differentiation and phosphorylation of CREB-1 and the related factor CREM-1 are stimulated by M-CSF in a SAPK2/p38-dependent manner...

..Our established system is applicable to inhibitor screening and drug discovery related to MSK1/MSK2...

..Stress signaling pathways might be an interesting pharmacologic target for differentiation therapy of malignant disease...

..Furthermore, chimeric analysis with p38beta (which does not bind to TAB1) revealed a previously unidentified locus of p38alpha comprising Thr218 and Ile275 ..

..and activation of RSK2 is mediated by the MAPK/ERK pathway, but that the Stress-Activated Protein Kinase 2 (SAPK2)/p38 pathway is also involved...

..AG17 treatment was accompanied by decreased levels of STAT3 phosphorylation, whereas NF-kappaB and p38/SAPK2 signaling were not inhibited...

..that following VEGF treatment of endothelial cells, VEGFR-2 is phosphorylated on Tyr1214 upstream of the Cdc42-SAPK2/p38-MAPKAP K2 pathway...

..Using adenovirus-mediated gene transfer technique, we further demonstrated that p38beta, but not p38alpha, is essential to protect the cells from TNF-alpha toxicity...

..These results indicate a critical role of p38/stress-activated protein kinase-2 and NF-kappaB-dependent phosphatase in macrophage hyporesponsiveness induced by microbial products that activate TLR2 and TLR4...

..We conclude that the mechanism by which curcumin modulates UV activation of HIV-LTR gene expression mainly involves the inhibition of NF-kappaB activation...

..are those that use the extracellular signal-regulated kinase (ERK1/2) or the stress-activated protein kinase (p38/SAPK2 or JNK/SAPK) pathways...

..The phosphorylation of HSP25 by the p38/SAPK2 pathway is known to be important for certain of its functions...

..These results may also shed light on the vital role of EDG-1 in vascular maturation...

..These results suggest that, in addition to viral dsRNA, stress signaling contributes to the regulation of cellular antiviral response...

....

..Moreover, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and overexpressed dominant negative p38beta decreased, whereas dominant negative p38delta increased, LPS-dependent induction of HO-1 gene expression...

..Mechanistic studies in vitro indicate that specific cadherins and immunoglobulin superfamily proteins exert some of their effects in an interdependent fashion by signaling from a multiprotein complex found at sites of cell-cell contact...

..Autocrine EGF receptor activation through TACE-mediated ectodomain shedding intimately links inflammation and cancer progression and may play a role in stress and conditions that relate to p38 MAP kinase activation...

..The activation of this salvage pathway is dependent on SAPK2/p38-mediated activation of IRES-dependent initiation of the cyclin D1 and c-MYC mRNAs, resulting in the ..

..Major signalling pathways used by eukaryotic cells to transduce extracellular signals into cellular responses impinge on the mitogen-activated protein kinases (MAPKs)...

..We observed the direct interaction of histone deacetylase (HDAC) 3, a class I histone deacetylase, with MAPK11 (p38 beta isoform) by West-Western-based screening analysis, pull-down assay, and two-hybrid system analysis...

..vitro by SAPK3/p38gamma, SAPK4/p38delta and JNK (c-Jun N-terminal kinase), but weakly by SAPK2a/p38alpha, SAPK2b/p38beta2 or ERK (extracellular-signal-regulated kinase) 2...

..By performing a thorough genetic analysis, we demonstrate that a signalling complex consisting of p38b and MK2 forms a branch of SAPK signalling that is required in the larval hindgut to prevent stress-dependent damage ..

..We investigated whether either the spinal isoform p38alpha or p38beta is involved in peripheral inflammation evoked pain state and increased expression of spinal COX-2...

..We also demonstrate that E2F1 downregulation by novel PKC isozymes requires activation of p38beta mitogen-activated protein kinase (MAPK)...

..Furthermore, we show that PRAK activates p53 by direct phosphorylation. We propose that phosphorylation of p53 by PRAK following activation of p38 MAPK by ras plays an important role in ras-induced senescence and tumor suppression...

..However, the relative contribution of the four p38 MAP kinases (p38alpha, p38beta, p38gamma and p38delta) to this process was unknown...

..of Fak, Src, Akt-1 and Erk1/2, a loss of Fak-Src association, and a sustained/enhanced activation of p38beta, which is required as apoptosis/anoikis driver; (2) PI3-K/Akt-1 up-regulates the expression of Bcl-X(L) and Mcl-1,..

..rats show high NEFA levels, we assessed PDX-1 and insulin mRNA expression, as well as PDX-1 and p38/stress activated protein kinase 2 (SAPK2) protein expression, in islets from young rats fed low (6%) or normal (17%; control) protein ..

..The wild-types of p38alpha, p38beta, p38gamma, and p38delta signal molecules all markedly downregulated promoter activity, which could be reversed by ..

..responses has been shown in a number of studies using chemical inhibitors, though the inhibitors also inhibit p38beta and perhaps some other enzymes...

....

..Similar manipulations of other Map kinases such as ERK1, JNK1 or JNK2 and p38alpha or p38beta were without effect...

..In contrast, blockade of p38 in SLO permeabilized cells did not affect the capacity of the cells to replenish their ATP stores...

..primarily in response to inflammatory cytokines and cellular stress, and inhibitors which target the p38alpha and p38beta MAPKs have shown potential for the treatment of inflammatory disease...

..of p38alpha by isoform-specific small interfering RNAs increased claudin-4 and -8 mRNAs, whereas silencing of p38beta only increased claudin-4 mRNA...

..mice with cardiac-specific expression of kinase dead (dominant negative) mutants of p38alpha (p38alphadn) or p38beta (p38betadn). Hearts were subjected to 20 min ischemia and 40 min reperfusion...

..in cell signaling such as p47, p38alpha, JNK, c-Yes, total PKC, and decreased the expression of molecules such as p38beta, ERK1/2, and XIAP relative to HIV-2 infection...

..In addition nilotinib has now been found to bind to both MAPK11 (p38beta) and MAPK12 (p38alpha), as well as with very high affinity to ZAK kinase...

..To examine the cellular distribution and location of p38alpha/beta isoforms in the lumbar spinal cord of the bone cancer pain rats...

..The present study further investigates involvement of the p38 MAPK pathway in IL-8's ability to block TRAIL-induced apoptosis in the ovarian surface epithelial cancer cell line, OVCAR3...

..Little is known of the signaling events implicated in the induction of human enterocytic anoikis. In the present study, we analyzed the role of the stress-activated protein kinase p38 in this process...

..p38alpha and C-terminal Flag-tagged p38beta were purified by Q-Sepharose fast flow, hydroxyapatite, and Q-Sepharose high-performance chromatography...

..These studies reveal a mechanism via which gp120 may differentially modulate the fate of activated and quiescent T cells in vivo...

..When combined with unique animal models, gene array analysis provides a useful approach for identifying and characterizing pathways involved in bladder inflammation...

..Since the phosphorylation of Ser-377 does not inhibit eEF2 kinase in vitro, our results suggest that anisomycin or TNF-alpha inhibit eEF2 kinase via the phosphorylation of Ser-359...

..Here we have developed a system to study the effects of five SAP kinases (SAPK1c/JNK1, SAPK2a/p38alpha, SAPK2b/p38beta, SAPK3/p38gamma and SAPK4/p38delta) on tau phosphorylation in intact cells...

..results from the activation of the mitogen-activated protein (MAP) kinase stress-activated protein kinase-2/p38 (SAPK2/p38), which, via MAP kinase-activated protein (MAPKAP) kinase-2/3, leads to the phosphorylation of the actin ..

..p42(MAPK)), c-Jun NH(2)-terminal kinases (JNKs), ERK5 (or BMK), and p38 MAPKs, including p38alpha (or CSBP-1), p38beta, p38gamma (or SAPK3 or ERK6), and p38delta?(or SAPK4)...

..In this study we show that human platelets contain the isoforms SAPK2a, SAPK2b, SAPK3 and SAPK4 as determined by immunoblotting with specific antibodies...

..protein was detected in skeletal muscle extracts that was phosphorylated rapidly by SAPK4/p38delta, but poorly by SAPK2/p38, SAPK3/p38gamma, SAPK1/JNK or extracellular signal-regulated kinase 2 (ERK2)...

..phosphospecific antibodies we showed that extracellular signal-regulated kinases 1 and 2 (ERK), SAPK1 (JNK), and SAPK2 (p38) are hyperosmotically activated in mIMCD cells...

..of primary fibroblasts cultured in fl-coll with increasing doses of SB203580, an inhibitor of p38alpha and p38beta, caused a bipolar pattern of MMP-1 expression...

....

..ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH(2)-terminal kinase-1, or p38beta activities differed little...

..through engagement of CD11b or CD11c results in the phosphorylation and activation of ERK1, ERK2, and p38/SAPK2 MAP kinases...

..In MAPK expression we found that unstimulated NKL cells have the following profile: ERK2>ERK6>p38gamma>p38beta>ERK1. ERK3, ERK3 rel, ERK5/ERK4 and p38delta were not expressed...

..Modulation of cell death pathways activated by pneumolysin may influence the outcome of pneumococcal meningitis...

..and SAP-1 at similar rates, but were far less effective than SAPK2a (also called RK/p38) or SAPK2b (also called p38beta) in activating MAPKAP kinase-2 and MAPKAP kinase-3...

..These findings suggest that alternative activation pathways contribute to the biological responses of p38alpha to various stimuli...

..Protein expression of the kinases was similar in trained and sedentary muscle. The increased aPKC activity in exercise-trained subjects could be important in explaining the enhanced insulin action in these individuals...

..AG490, a JAK inhibitor, blocked TRAIL expression induced by IFN-gamma. SB203580, a specific p38alpha and p38beta2 MAPK inhibitor, decreased the TRAIL expression induced by IFN-gamma...

..Intraperitoneal injection of SB202190, an inhibitor of p38alpha and p38beta MAPK activity, markedly increased the ability of DN-14-3-3 mice to compensate for pressure overload, with ..

..g. p38alpha and p38beta, serves as a crucial determinant of myocyte fate...

..in our lab; (b) western blots from traumatized brain show activation of the MAP kinase pathways ERK and SAPK2/p38; (c) the ERK/MAP kinase pathway upregulates MMP in vitro; (d) MMP activation occurs after trauma in vivo; (e) ..

..objective is to determine if the p38 kinase that is activated during hypoxia tolerance corresponds to p38alpha, p38beta, p38gamma, or p38delta...

..The goal of this research is to investigate the roles for p38alpha and p38beta, two major isoforms expressed in endothelial cells (ECs), in the regulation of EC activities involved in ..

..We hope that identification of proteins important in maintaining a non-leaky state will assist in discovering a treatment for patients suffering from lung edema. ..

..Results from these studies will define the signal transduction pathway mediating the senescence response and tumor suppression, and may lead to the development of novel cancer therapies targeting the senescence pathway. ..

..These studies will not only offer insights into the diverse pathways leading to the loss of TGFbeta sensitivity in tumors, but also reveal novel roles of MDM2 in tumorigenesis. ..

....

..abstract_text> ..

..abstract_text> ..

....

..We hope that identification of proteins important in maintaining a non-leaky state will assist in discovering a treatment for patients suffering from lung edema. ..

..Information generated by this study should elucidate whether bladder inflammatory responses, regardless of etiology, occur via a common mechanism or whether the endpoints are specific for each stimulus. ..

..We hope that identification of proteins important in maintaining a non-leaky state will assist in discovering a treatment for patients suffering from lung edema. ..

..Scott-Hultgren (Washington U) will discuss the molecular basis of persistent bladder infections. The bladder cancer discussion will be chaired by Drs. Robert Hurst (Oklahoma U) and Jenny Southgate (U. York). ..

....

..These studies will identify and define the important mechanisms involved in bladder inflammation and provide new insights for developing treatment strategies for cystitis. ..

....

..of p67 LBP and the integrin alpha6 to lymphocyte laminin-specific adherence? and (4) What are the contributions of p67 LBP and alpha6 to laminin-mediated lamellipod formation, locomotion, and transendothelial migration? ..