Activation of MAP kinase and translocation with HSP27 in bombesin-induced contraction of rectosigmoid smooth muscle

1995 ◽  
Vol 269 (5) ◽  
pp. G683-G691 ◽  
Author(s):  
H. Yamada ◽  
J. Strahler ◽  
M. J. Welsh ◽  
K. N. Bitar
Keyword(s):  
Smooth Muscle ◽  
Map Kinase ◽  
Resting Cells ◽  
Kinase Activation ◽  
Sustained Contraction ◽  
Contraction Map ◽  
Map Kinase Cascade ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

We have investigated whether mitogen-activated protein (MAP) kinase cascade is essential for sustained contraction of smooth muscle cells of the rabbit rectosigmoid. We have identified MAP kinase as one of the enzymes activated by bombesin, performed immunologic studies blocking the activation of MAP kinase, and conducted confocal localization of MAP kinase in relation to heat-shock protein (HSP27), postulated to be involved in the sustained contraction of smooth muscle. Immunoblotting revealed two forms of MAP kinase (42 and 44 kDa). Activation of MAP kinase by bombesin was rapid, reaching a maximum in 30 s and subsequently declining. [D-Phe6,Leu13,psi(CH2NH),Phe14]BN-(6-14), a potent bombesin antagonist, and protein kinase C (PKC) inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, calphostin C, and chelerythrine inhibited the increase in MAP kinase induced by bombesin. Immunofluorescent dual labeling and confocal microscopy indicate that these two proteins are closely distributed in resting cells and that during bombesin-induced contraction MAP kinase translocates accompanied by HSP27. In conclusion, a series of events involving PKC activation, MAP kinase activation, and MAP kinase-HSP27 translocation could be the signaling pathway involved in bombesin-induced sustained contraction.

scholarly journals Trypsin stimulates proteinase-activated receptor-2-dependent and -independent activation of mitogen-activated protein kinases

1996 ◽  
Vol 320 (3) ◽  
pp. 939-946 ◽  
Author(s):  
Christopher M. BELHAM ◽  
Rothwelle J. TATE ◽  
Pamela H. SCOTT ◽  
Alan D. PEMBERTON ◽  
Hugh R. P. MILLER ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Muscle Cells ◽  
Peptide Sequence ◽  
Pcr Analysis ◽  
Kinase Activation ◽  
Map Kinase Cascade ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

We have examined protease-mediated activation of the mitogen-activated protein (MAP) kinase cascade in rat aortic smooth-muscle cells and bovine pulmonary arterial fibroblasts. Exposure of smooth-muscle cells to trypsin evoked rapid and transient activation of c-Raf-1, MAP kinase kinase 1 and 2 and MAP kinase that was sensitive to inhibition by soybean trypsin inhibitor. The actions of trypsin were closely mimicked by the proteinase-activated receptor 2 (PAR-2)-activating peptide sequence SLIGRL but not LSIGRL. Peak MAP kinase activation in response to both trypsin and SLIGRL was also dependent on concentration, with EC50 values of 12.1±3.4 nM and 62.5±4.5 µM respectively. Under conditions where MAP kinase activation by SLIGRL was completely desensitized by prior exposure of smooth-muscle cells to the peptide, trypsin-stimulated MAP kinase activity was markedly attenuated (78.9±15.1% desensitization), whereas the response to thrombin was only marginally affected (16.6±12.1% desensitization). Trypsin and SLIGRL also weakly stimulated the activation of the MAP kinase homologue p38 in smooth-muscle cells without any detectable activation of c-Jun N-terminal kinase. Strong activation of the MAP kinase cascade and modest activation of p38 by trypsin were also observed in fibroblasts, although in this cell type these effects were not mimicked by SLIGRL nor by the thrombin receptor-activating peptide SFLLRNPNDKYEPF. Reverse transcriptase–PCR analysis confirmed the presence of PAR-2 mRNA in smooth-muscle cells but not fibroblasts. Our results suggest that in vascular smooth-muscle cells, trypsin stimulates the activation of the MAP kinase cascade relatively selectively, in a manner consistent with an interaction with the recently described PAR-2. Activation of MAP kinase by trypsin in vascular fibroblasts, however, seems to be independent of PAR-2 and occurs by an undefined mechanism possibly involving novel receptor species.

scholarly journals Combined computational and experimental analysis reveals mitogen-activated protein kinase–mediated feedback phosphorylation as a mechanism for signaling specificity

2012 ◽  
Vol 23 (19) ◽  
pp. 3899-3910 ◽  
Author(s):  
Nan Hao ◽  
Necmettin Yildirim ◽  
Michal J. Nagiec ◽  
Stephen C. Parnell ◽  
Beverly Errede ◽  
...  
Keyword(s):  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Invasive Growth ◽  
Kinase Activation ◽  
Signaling Specificity ◽  
Map Kinase Cascade ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Physiological Outcomes

Different environmental stimuli often use the same set of signaling proteins to achieve very different physiological outcomes. The mating and invasive growth pathways in yeast each employ a mitogen-activated protein (MAP) kinase cascade that includes Ste20, Ste11, and Ste7. Whereas proper mating requires Ste7 activation of the MAP kinase Fus3, invasive growth requires activation of the alternate MAP kinase Kss1. To determine how MAP kinase specificity is achieved, we used a series of mathematical models to quantitatively characterize pheromone-stimulated kinase activation. In accordance with the computational analysis, MAP kinase feedback phosphorylation of Ste7 results in diminished activation of Kss1, but not Fus3. These findings reveal how feedback phosphorylation of a common pathway component can limit the activity of a competing MAP kinase through feedback phosphorylation of a common activator, and thereby promote signal fidelity.

scholarly journals Structurally unique interaction of RBD-like and PH domains is crucial for yeast pheromone signaling

2013 ◽  
Vol 24 (3) ◽  
pp. 409-420 ◽  
Author(s):  
Volodymyr Yerko ◽  
Traian Sulea ◽  
Irena Ekiel ◽  
Doreen Harcus ◽  
Jason Baardsnes ◽  
...  
Keyword(s):  
Map Kinase ◽  
Ph Domain ◽  
Yeast Saccharomyces Cerevisiae ◽  
Kinase Activation ◽  
Functional Studies ◽  
Pheromone Signaling ◽  
Map Kinase Cascade ◽  
Evolutionarily Conserved ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

The Ste5 protein forms a scaffold that associates and regulates the components of the mitogen-activated protein (MAP) kinase cascade that controls mating-pheromone-mediated signaling in the yeast Saccharomyces cerevisiae. Although it is known that the MEK kinase of the pathway, Ste11, associates with Ste5, details of this interaction have not been established. We identified a Ras-binding-domain-like (RBL) region in the Ste11 protein that is required specifically for the kinase to function in the mating pathway. This module is structurally related to domains in other proteins that mediate Ras-MAP kinase kinase kinase associations; however, this RBL module does not interact with Ras, but instead binds the PH domain of the Ste5 scaffold. Structural and functional studies suggest that the key role of this PH domain is to mediate the Ste5–Ste11 interaction. Overall these two evolutionarily conserved modules interact with each other through a unique interface, and thus in the pheromone pathway the structural context of the RBL domain contribution to kinase activation has been shifted through a change of its interaction partner from Ras to a PH domain.

scholarly journals A Novel Regulatory Mechanism in the Mitogen-activated Protein (MAP) Kinase Cascade

1997 ◽  
Vol 272 (51) ◽  
pp. 32642-32648 ◽  
Author(s):  
Makoto Fukuda ◽  
Isamu Gotoh ◽  
Makoto Adachi ◽  
Yukiko Gotoh ◽  
Eisuke Nishida
Keyword(s):  
Map Kinase ◽  
Regulatory Mechanism ◽  
Map Kinase Cascade ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

scholarly journals Regulation of cotton (Gossypium hirsutum ) drought responses by mitogen-activated protein (MAP) kinase cascade-mediated phosphorylation of GhWRKY59

2017 ◽  
Vol 215 (4) ◽  
pp. 1462-1475 ◽  
Author(s):  
Fangjun Li ◽  
Maoying Li ◽  
Ping Wang ◽  
Kevin L. Cox ◽  
Liusheng Duan ◽  
...  
Keyword(s):  
Gossypium Hirsutum ◽  
Map Kinase ◽  
Map Kinase Cascade ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

scholarly journals The Stress-activated Mitogen-activated Protein Kinase Signaling Cascade Promotes Exit from Mitosis

2006 ◽  
Vol 17 (7) ◽  
pp. 3136-3146 ◽  
Author(s):  
Vladimír Reiser ◽  
Katharine E. D’Aquino ◽  
Ly-Sha Ee ◽  
Angelika Amon
Keyword(s):  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
Hypertonic Stress ◽  
Map Kinase Cascade ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Early Anaphase ◽  
Kinase Cascade ◽  
Protein Kinase Signaling

In budding yeast, a signaling network known as the mitotic exit network (MEN) triggers exit from mitosis. We find that hypertonic stress allows MEN mutants to exit from mitosis in a manner dependent on the high osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase cascade. The HOG pathway drives exit from mitosis in MEN mutants by promoting the activation of the MEN effector, the protein phosphatase Cdc14. Activation of Cdc14 depends on the Cdc14 early anaphase release network, a group of proteins that functions in parallel to the MEN to promote Cdc14 function. Notably, exit from mitosis is promoted by the signaling branch defined by the Sho1 osmosensing system, but not by the Sln1 osmosensor of the HOG pathway. Our results suggest that the stress MAP kinase pathway mobilizes programs to promote completion of the cell cycle and entry into G1 under unfavorable conditions.

scholarly journals Role of a Mitogen-Activated Protein Kinase Cascade in Ion Flux-Mediated Turgor Regulation in Fungi

2006 ◽  
Vol 5 (3) ◽  
pp. 480-487 ◽  
Author(s):  
Roger R. Lew ◽  
Natalia N. Levina ◽  
Lana Shabala ◽  
Marinela I. Anderca ◽  
Sergey N. Shabala
Keyword(s):  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Turgor Regulation ◽  
Map Kinase Cascade ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Protein Kinase Cascade

ABSTRACT Fungi normally maintain a high internal hydrostatic pressure (turgor) of about 500 kPa. In response to hyperosmotic shock, there are immediate electrical changes: a transient depolarization (1 to 2 min) followed by a sustained hyperpolarization (5 to 10 min) prior to turgor recovery (10 to 60 min). Using ion-selective vibrating probes, we established that the transient depolarization is due to Ca2+ influx and the sustained hyperpolarization is due to H+ efflux by activation of the plasma membrane H+-ATPase. Protein synthesis is not required for H+-ATPase activation. Net K+ and Cl− uptake occurs at the same time as turgor recovery. The magnitude of the ion uptake is more than sufficient to account for the osmotic gradients required for turgor to return to its original level. Two osmotic mutants, os-1 and os-2, homologs of a two-component histidine kinase sensor and the yeast high osmotic glycerol mitogen-activated protein (MAP) kinase, respectively, have lower turgor than the wild type and do not exhibit the sustained hyperpolarization after hyperosmotic treatment. The os-1 mutant does not exhibit all of the wild-type turgor-adaptive ion fluxes (Cl− uptake increases, but net K+ flux barely changes and net H+ efflux declines) (os-2 was not examined). Both os mutants are able to regulate turgor but at a lower level than the wild type. Our results demonstrate that a MAP kinase cascade regulates ion transport, activation of the H+-ATPase, and net K+ and Cl− uptake during turgor regulation. Other pathways regulating turgor must also exist.

scholarly journals A role for MAP kinase in differentiated smooth muscle contraction evoked by α-adrenoceptor stimulation

1998 ◽  
Vol 275 (4) ◽  
pp. C1081-C1086 ◽  
Author(s):  
Chantal Dessy ◽  
Inkyeom Kim ◽  
Carrie L. Sougnez ◽  
Regent Laporte ◽  
Kathleen G. Morgan
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Map Kinase ◽  
Specific Inhibitor ◽  
Smooth Muscle Contraction ◽  
Isometric Tension ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein

The purpose of this study was to investigate the potential role of mitogen-activated protein (MAP) kinase in smooth muscle contraction by monitoring MAP kinase activation, caldesmon phosphorylation, and contractile force during agonist stimulation. Isometric tension in response to KCl and phenylephrine (PE) was measured from strips of ferret aorta. MAP kinase activation was monitored by Western blot using a phosphospecific p44/p42 MAP kinase antibody. Caldesmon phosphorylation was assessed using specific phosphocaldesmon antibodies. We report here that treatment of smooth muscle strips with PD-098059, a specific inhibitor of MAP kinase kinase, did not detectably modify the KCl-evoked contraction but significantly inhibited the contraction to PE in the absence of extracellular Ca2+. In this experimental condition, where the contraction occurs in the absence of increases in 20-kDa myosin light chain phosphorylation, PD-098059 also inhibited significantly MAP kinase and caldesmon phosphorylation. Collectively, these results demonstrate a direct cause-and-effect relationship between MAP kinase activation and Ca2+-independent smooth muscle contraction and support the concept of caldesmon phosphorylation as the missing link between both events.

Genetic Analysis of rolled, Which Encodes a Drosophila Mitogen-Activated Protein Kinase

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 763-771 ◽  
Author(s):  
Young-Mi Lim ◽  
Kimiko Nishizawa ◽  
Yoshimi Nishi ◽  
Leo Tsuda ◽  
Yoshihiro H Inoue ◽  
...  
Keyword(s):  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Female Sterility ◽  
Tor Signaling ◽  
Map Kinase Cascade ◽  
Dominant Female ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

Abstract Genetic and molecular characterization of the dominant suppressors of D-rafC110 on the second chromosome identified two gain-of-function alleles of rolled (rl), which encodes a mitogen-activated protein (MAP) kinase in Drosophila. One of the alleles, rlSu23, was found to bear the same molecular lesion as rlSem, which has been reported to be dominant female sterile. However, rlSu23 and the current stock of rlSem showed only a weak dominant female sterility. Detailed analyses of the rl mutations demonstrated moderate dominant activities of these alleles in the Torso (Tor) signaling pathway, which explains the weak dominant female sterility observed in this study. The dominant rl mutations failed to suppress the terminal class maternal-effect mutations, suggesting that activation of Rl is essential, but not sufficient, for Tor signaling. Involvement of rl in cell proliferation was also demonstrated by clonal analysis. Branching and integration of signals in the MAP kinase cascade is discussed.

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