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Query: UNIPROT:Q17RS7 (Gen)
 130,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases that are activated in response to a variety of stimuli. Here we report the isolation of an alfalfa cDNA encoding a functional MAP kinase, termed MMK2. The predicted amino acid sequence of MMK2 shares 65% identity with a previously identified alfalfa MAP kinase, termed MMK1. Both alfalfa cDNA clones encode functional kinases when expressed in bacteria, undergoing autophosphorylation and activation to phosphorylate myelin basic protein in vitro. However, only MMK2 was able to phosphorylate a 39 kDa protein from the detergent-resistant cytoskeleton of carrot cells. The distinctiveness of MMK2 was further shown by complementation analysis of three different MAP kinase-dependent yeast pathways; this revealed a highly specific replacement of the yeast MPK1(SLT2) kinase by MMK2, which was found to be dependent on activation by the upstream regulators of the pathway. These results establish the existence of MAP kinases with different characteristics in higher plants, suggesting the possibility that they could mediate different cellular responses.
Mol Gen Genet 1995 Oct 25
PMID:MMK2, a novel alfalfa MAP kinase, specifically complements the yeast MPK1 function. 747 71

A cDNA (cNPK2) that encodes a protein of 518 amino acids was isolated from a library prepared from poly(A)+ RNAs of tobacco cells in suspension culture. The N-terminal half of the predicted NPK2 protein is similar in amino acid sequence to the catalytic domains of kinases that activate mitogen-activated protein kinases (designated here MAPKKs) from various animals and to those of yeast homologs of MAPKKs. The N-terminal domain of NPK2 was produced as a fusion protein in Escherichia coli, and the purified fusion protein was found to be capable of autophosphorylation of threonine and serine residues. These results indicate that the N-terminal domain of NPK2 has activity of a serine/threonine protein kinase. Southern blot analysis showed that genomic DNAs from various plant species, including Arabidopsis thaliana and sweet potato, hybridized strongly with cNPK2, indicating that these plants also have genes that are closely related to the gene for NPK2. The structural similarity between the catalytic domain of NPK2 and those of MAPKKs and their homologs suggests that tobacco NPK2 corresponds to MAPKKs of other organisms. Given the existence of plant homologs of an MAP kinase and tobacco NPK1, which is structurally and functionally homologous to one of the activator kinases of yeast homologs of MAPKK (MAPKKKs), it seems likely that a signal transduction pathway mediated by a protein kinase cascade that is analogous to the MAP kinase cascades proposed in yeasts and animals, is also conserved in plants.
Mol Gen Genet 1995 Feb 20
PMID:A tobacco protein kinase, NPK2, has a domain homologous to a domain found in activators of mitogen-activated protein kinases (MAPKKs). 789 53

The HST7 gene of Candida albicans encodes a protein with structural similarity to MAP kinase kinases. Expression of this gene in Saccharomyces cerevisiae complements disruption of the Ste7 MAP kinase kinase required for both mating in haploid cells and pseudohyphal growth in diploids. However, Hst7 expression does not complement loss of either the Pbs2 (Hog4) MAP kinase kinase required for response to high osmolarity, or loss of the Mkk1 and Mkk2 MAP kinase kinases required for proper cell wall biosynthesis. Intriguingly, HST7 acts as a hyperactive allele of STE7; expression of Hst7 activates the mating pathway even in the absence of upstream signaling components including the Ste7 regulator Ste11, elevates the basal level of the pheromone-inducible FUS1 gene, and amplifies the pseudohyphal growth response in diploid cells. Thus Hst7 appears to be at least partially independent of upstream activators or regulators, but selective in its activity on downstream target MAP kinases. Creation of Hst7/Ste7 hybrid proteins revealed that the C-terminal two-thirds of Hst7, which contains the protein kinase domain, is sufficient to confer this partial independence of upstream activators.
Mol Gen Genet 1995 Dec 20
PMID:Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans. 854 26

Saccharomyces cerevisiae mutants which exhibit phenotypes (calcium resistance and vanadate sensitivity) similar to those of calcineurin-deficient mutants were isolated. The mutants were classified into four complementation groups (crv1,2,3 and 4). Crv1 was allelic to cnb1, a mutation in the regulatory subunit of calcineurin. The nucleotide sequences of CRV2 and CRV3 genes which complemented the crv2 and crv3 mutations, respectively, are identical to those of BCK1/SLK1/SKC1/SSP31 and MPK1/SLT2, respectively, which are both involved in the MAP kinase cascade. A calcineurin-deletion mutation (delta cnb1), which by itself has no detectable effect on growth and morphology, enhanced some phenotypes (slow growth and morphological abnormality) of crv2 and crv3 mutants. These phenotypes of crv2 and crv3 mutants were partially suppressed by Ca2+ or by overproduction of the calcineurin subunits (Cmp2 and Cnb1). Like the calcineurin-deficient mutant, crv2 and crv3 mutants were defective in recovery from alpha-factor-induced growth arrest. The defect in recovery of the delta cnb1 mutant was suppressed by overexpression of MPK1. These results indicated that the calcineurin-mediated and the Mpk1- (Bck1-) mediated signaling pathways act in parallel to regulate functionally redundant cellular events important for growth.
Mol Gen Genet 1996 May 23
PMID:Genetic evidence for the functional redundancy of the calcineurin- and Mpk1-mediated pathways in the regulation of cellular events important for growth in Saccharomyces cerevisiae. 866 32

The two-hybrid system for the identification of protein-protein interactions was used to screen for proteins that interact in vivo with the Saccharomyces cerevisiae Pkc1 protein, a homolog of mammalian protein kinase C. Four positive clones were isolated that encoded portions of the protein kinase Mkk1, which acts downstream of Pkc1p in the PKC1-mediated signalling pathway. Subsequently, Pkc1p and the other PKC1 pathway components encoding members of a MAP kinase cascade, Bck1p (a MEKK), Mkk1p, Mkk2p (two functionally homologous MEKs), and Mpk1p (a MAP kinase), were tested pairwise for interaction in the two-hybrid assay. Pkc1p interacted specifically with small N-terminal deletions of Mkk1p, and no interaction between Pkc1p and any of the other known pathway components could be detected. Interaction between Pkc1p and Mkk1p, however, was found to be independent of Mkk1p kinase activity. Bck1p was also found to interact with Mkk1p and Mkk2p, and the interaction required only the predicted C-terminal catalytic domain of Mkk1p. Furthermore, we detected protein-protein interactions between two Bck1p molecules via their N-terminal regions. Finally, Mkk2p and Mpk1p also interacted in the two-hybrid assay. These results suggest that the members of the PKC1-mediated MAP kinase cascade form a complex in vivo and that Pkc1p is capable of directly interacting with at least one component of this pathway.
Mol Gen Genet 1996 Jul 26
PMID:Protein-protein interactions in the yeast PKC1 pathway: Pkc1p interacts with a component of the MAP kinase cascade. 875 99

Simian virus 40 (SV40) binding to growth-arrested cells activated an intracellular signalling pathway that induced the up-regulation of the primary response genes c-myc, c-jun and c-sis within 30 min and of JE within 90 min. The up-regulation of the primary response genes occurred in the presence of cycloheximide and when UV-inactivated SV40 was adsorbed to cells. SV40 binding did not activate Raf or mitogen-activated protein kinase (MAP/ERK1), or mobilize intracellular Ca2+. The SV40-induced up-regulation of c-myc and c-jun was blocked by the tyrosine kinase inhibitor, genistein, and by the protein kinase C (PKC) inhibitor, calphostin C, but not by expression of the MAP kinase-specific phosphatase, MKP-1. These results suggest that the SV40-induced signalling pathway includes the activities of a tyrosine kinase and a Ca(2+)-independent isoform of PKC, but not of Raf or MAP kinase. Finally, SV40 infectious entry into cells was specifically and reversibly blocked by genistein.
J Gen Virol 1996 Sep
PMID:Extracellular simian virus 40 induces an ERK/MAP kinase-independent signalling pathway that activates primary response genes and promotes virus entry. 881 Oct 17

We are developing budding yeast, Saccharomyces cerevisiae, as a genetic system for the study of tolerance to the trivalent aluminum cation (Al3+). We have isolated eight mutants that are more sensitive to Al3+ than the wild type. Each mutant represented a different complementation group. A number of the mutants were pleiotropic, and showed defects in other stress responses, changes in tolerance to other metal cations, or abnormal morphology. Two mutants also showed increased dependence on supplemental Mg2+ and Ca2+. One mutant with a relatively specific sensitivity to Al3+ was chosen for molecular complementation. Normal Al3+ tolerance was restored by expression of the MAP kinase gene SLT2. Strains carrying deletions of the SLT2 gene, or of the gene for the corresponding MAP kinase kinase SLK1, showed sensitivity to Al3+. These results indicate that the SLT2 MAP kinase signal transduction pathway is required for yeast to sense and respond to Al3+ stress.
Mol Gen Genet 1997 Mar 18
PMID:Aluminum-sensitive mutants of Saccharomyces cerevisiae. 910 91

The purpose of the studies included in this chapter was to examine the role of the actin network in the propagation of insulin action leading to stimulation of glucose transport and activation of the mitogen-activated protein kinase cascade. The active insulin receptor phosphorylates tyrosine residues of intracellular proteins such as the insulin receptor substrate-1 (IRS-1) which acts as docking sites for molecules containing Src homology 2 (SH2) domains. One such molecule is phosphatidylinositol 3-kinase (PI 3-kinase) which becomes activated by binding to IRS-1. PI 3-kinase activity is required for the insulin-stimulation of glucose transport and glycogen synthesis. Grb2, a small adaptor molecule, can bind IRS-1 and, through the guanine nucleotide exchange factor Sos, leads to the activation of the small GTP binding protein Ras. Through a cascade of protein kinases, activation of Ras results in activation of the Erk 1 and 2 mitogen-activated protein kinases (MAPKs) which appear to control important nuclear and metabolic events. To investigate the role of the actin network in the propagation of insulin action leading to stimulation of glucose transport and the activation of the Erk MAPKs, we used the fungal metabolite cytochalasin D which disassembles the actin network. Actin disassembly abolished almost completely the ability of insulin to increase the rate of glucose transport into L6 muscle cells (myotubes) through prevention of the insulin-induced recruitment of glucose transporters to the plasma membrane which is the event that mediates the increase in the rate of transport. Actin disassembly did not affect either the insulin-mediated phosphorylation of IRS-1, the association of PI 3-kinase with this molecule, or the activation of IRS-1-associated PI 3-kinase. These results were also verified in another insulin responsive cell line, the 3T3-L1 adipocytes. In these cells, actin disassembly inhibited the insulin-induced recruitment of PI 3-kinase to intracellular membranes containing glucose transporters. Moreover, actin disassembly abolished the insulin-mediated phosphorylation of the Erk MAPKs. We conclude that the cellular actin network of insulin responsive cells is not required for the activation of PI 3-kinase but prevents its cellular redistribution. In contrast, intact actin filaments are essential for the propagation of insulin signals leading to the the activation of the MAPKs.
Soc Gen Physiol Ser 1997
PMID:Involvement of the actin network in insulin signalling. 921 Feb 35

The Saccharomyces cerevisiae crv mutants (crv1, 2, 3 and 4) exhibit phenotypes, such as calcium resistance and vanadate sensitivity, which are apparently similar to those of calcineurin-deficient mutants. We have cloned and characterized the CRV4 gene that complements all the phenotypes of the crv4 mutant. DNA sequencing revealed that CRV4 is identical to the previously cloned gene TTP1, which encodes a type II membrane protein of unknown function. Deletion of CRV4/TTP1 causes no obvious phenotype except for Ca2+ resistance and vanadate sensitivity, but is synthetically lethal in combination with a deletion of MPK1, in a manner which is suppressible by the addition of an osmotic stabilizer. In medium containing sorbitol as an osmotic stabilizer, the enb1 mpk1 ttp1 triple mutant exhibits a more severe growth defect than does any of the double mutants enb1 ttp1, enb1 mpk1 or mpk1 ttp1. A high Ca2+ concentration (50 mM) or a constitutively active form of calcineurin partially suppresses the growth defect of the mpk1 ttp1 double mutant. These results indicate that Ttp1 participates in a cellular event essential for growth and morphogenesis, in parallel with the pathways involving Mpk1 MAP kinase and calcineurin.
Mol Gen Genet 1997 Nov
PMID:Yeast Crv4/Ttp1, a predicted type II membrane protein, is involved in an event important for growth, functionally overlapping with the event regulated by calcineurin- and Mpk1-mediated pathways. 941 31

1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth muscle cells (VSMC) and stimulates several events that are important for cell proliferation: DNA synthesis, protein synthesis, increase of cell number, immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2. Receptor characterization indicates mitogenic effects of both P2U and P2Y receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1, MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF, bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II, endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine, and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous arteries and veins. 6. The trophic effects on VSMC and the abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of atherosclerosis, neointima-formation after angioplasty, and possibly hypertension.
Gen Pharmacol 1998 Jul
PMID:Extracellular ATP: a growth factor for vascular smooth muscle cells. 959 70


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