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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During meiotic maturation or after fertilization of invertebrate and vertebrate oocytes, many of the quiescent stored mRNAs are recruited into polysomes. In the clam, Spisula solidissima, such masked messages include the abundant mRNAs encoding cyclin A and the small subunit of ribonucleotide reductase. We have previously shown that mRNA-specific unmasking of these two messages can be achieved in vitro, in oocyte cell-free extracts, by the addition of antisense RNAs corresponding to a fairly short (130-140 nucleotides) segment in their cognate 3' untranslated regions. We postulated that the antisense RNAs prevented the binding of a masking repressor protein (Standart et al., 1990). Here we report UV-crosslinking and gel retardation studies which show that the masking portions of the translationally regulated mRNAs bind an oocyte protein of 82 kDa (p82), which is phosphorylated after fertilization. This modification was accompanied by altered RNP complex formation in gel retardation assays. These changes presumably reflect the activation of translation of the masked mRNAs. The role of p82 phosphorylation in maternal mRNA unmasking was assessed in a novel in vitro activation system developed from clam oocytes, based upon the natural rise in pH which accompanies fertilization. Concomitant with mRNA unmasking, several kinases, including cdc2 and MAP kinases were activated in this system, as was p82 phosphorylation. Inhibitors of serine/threonine kinases, including 6-DMAP, staurosporine, and H7 inhibited p82 phosphorylation, whereas inhibitors of tyrosine kinases, protein kinase C, cAMP-dependent protein kinase, and p70s6k did not prevent this modification. A specific inhibitor of cdc2 kinase, p27Kip1, prevented p82 phosphorylation and translational activation, strongly suggesting that p82 modification is required for unmasking.
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PMID:Unmasking mRNA in clam oocytes: role of phosphorylation of a 3' UTR masking element-binding protein at fertilization. 857 30

The Tpl-2 protein serine/threonine kinase was originally identified, in a C-terminally deleted form, as the product of an oncogene associated with the progression of Moloney murine leukemia virus-induced T cell lymphomas in rats. The kinase domain of Tpl-2 is homologous to the Saccharomyces cerevisiae gene product, STE11, which encodes a MAP kinase kinase kinase. This suggested that Tpl-2 might have a similar activity. Consistent with this hypothesis, immunoprecipitated Tpl-2 and Tpl-2deltaC (a C-terminally truncated mutant) phosphorylated and activated recombinant fusion proteins of the mammalian MAP kinase kinases, MEK-1 and SEK-1, in vitro. Furthermore, transfection of Tpl-2 into COS-1 cells or Jurkat T cells. markedly activated the MAP kinases, ERK-1 and SAP kinase (JNK), which are substrates for MEK-1 and SEK-1, respectively. Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1.
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PMID:Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. 863 3

Aminopeptidases are exopeptidases that selectively release N-terminal amino acid residues from polypeptides and proteins. Bacteria display several aminopeptidasic activities which may be localised in the cytoplasm, on membranes, associated with the cell envelope or secreted into the extracellular media. Studies on the bacterial aminopeptide system have been carried out over the past three decades and are significant in fundamental and biotechnological domains. At present, about one hundred bacterial aminopeptidases have been purified and biochemically studied. About forty genes encoding aminopeptidases have also been cloned and characterised. Recently, the three-dimensional structure of two aminopeptidases, the methionine aminopeptidase from Escherichia coli and the leucine aminopeptidase from Aeromonas proteolytica, have been elucidated by crystallographic studies. Most of the quoted studies demonstrate that bacterial aminopeptidases generally show Michaelis-Menten kinetics and can be placed into either of two categories based on their substrate specificity: broad or narrow. These enzymes can also be classified by another criterium based on their catalytic mechanism: metallo-, cysteine- and serine-aminopeptidases, the former type being predominant in bacteria. Aminopeptidases play a role in several important physiological processes. It is noteworthy that some of them take part in the catabolism of exogenously supplied peptides and are necessary for the final steps of protein turnover. In addition, they are involved in some specific functions, such as the cleavage of N-terminal methionine from newly synthesised peptide chains (methionine aminopeptidases), the stabilisation of multicopy ColE1 based plasmids (aminopeptidase A) and the pyroglutamyl aminopeptidase (Pcp) present in many bacteria and responsible for the cleavage of the N-terminal pyroglutamate.
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PMID:Bacterial aminopeptidases: properties and functions. 870 9

The family of MAP kinases consists of several subgroups of serine/threonine protein kinases. Together with their activating kinases, they function to regulate cellular responses to diverse extracellular signals, including osmotic stress, heat shock, proinflammatory cytokines, and mitogens. It is now clear that as in yeast, separate MAP kinase cascades exist in mammalian cells, responding selectively to different stimuli by phosphorylating cytoplasmic components and nuclear transcription factors. Down-regulation of MAP kinase pathways may occur through dephosphorylation by serine/threonine phosphatases, tyrosine phosphatases, or dual-specificity phosphatases and through feedback inhibitory mechanisms that involve the phosphorylation of upstream kinases. The functional integrity of each MAP kinase cascade is thought to be established and maintained by specific molecular interactions both between the kinases and with cytoplasmic anchors that nucleate complex formation. The recent demonstration that a series of pyridinyl-imidazole compounds can bind and inhibit certain MAP kinases suggests that other MAP kinase subgroups may also be susceptible to synthetic compounds. Drugs that selectively down-regulate MAP kinase cascades could prove to be valuable as therapeutic agents in the control of malignant disease.
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PMID:The growing family of MAP kinases: regulation and specificity. 879 86

Microtubule-associated proteins can influence the organization, stability and dynamics of microtubules. We characterize a novel protein that associates with microtubules as assessed by immunofluorescence, immunoelectron microscopy, and co-sedimentation. The protein is expressed heavily in embryonic neurons and, to a lesser extent, in epithelial and mesodermal cells. The cDNA sequence predicts a protein of 1,547 amino acids and approximately 170 kDa. Immunoblot of embryo lysate demonstrates bands of approximately 240 and 260 kDa. The predicted amino acid sequence contains 77 potential serine/threonine phosphorylation sites. A distinctive feature is a predicted alpha-helical central domain comprising 21 identical repeats of an 11 amino acid sequence (PLEELRKDAAE). The protein is thermostable and has two major charge-domains: the amino-terminal 80% has an estimated pI of 4.0 and the carboxy-terminal 20%, a pI of 12.2. The protein shares several general biochemical and molecular features of MAPs, but its sequence is not similar to that of any described MAP.
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PMID:Blackjack, a novel protein associated with microtubules in embryonic neurons. 879 36

Karyophilic and acidic clusters were found in most nonmembrane serine/threonine protein kinases whose primary structure was examined. These karyophilic clusters might mediate the anchoring of the kinase molecules to transporter proteins for their regulated nuclear import and might constitute the nuclear localization signals (NLS) of the kinase molecules. In contrast to protein transcription factors that are exclusively nuclear possessing strong karyophilic peptides composed of at least four arginines (R) and lysines (K) within an hexapeptide flanked by proline and glycine helix-breakers, protein kinases often contain one histidine and three K+R residues; this is proposed to specify a weak NLS structure resulting in the nuclear import of a fraction of the total cytoplasmic kinase molecules as well as in their weak retention in the different ionic strength nuclear environment. Putative NLS peptides in protein kinases may also contain hydrophobic or bulky aromatic amino acids proposed to further diminish their capacity to act as strong NLS. Most kinases lacking karyophilic clusters (c-Mos, v-Mos, sea star MAP, and yeast KIN28, SRA1, SRA3, TPK1, TPK2) also lack acidic clusters, which is in contrast to most kinases containing both acidic and karyophilic peptides; this and the presence of R/K clusters in the transporter proteins supports a role of acidic clusters on kinases in nuclear import. Cyclins B lack karyophilic signals and are proposed to be imported into nuclei via their association with Cdc2.
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PMID:Nuclear import of protein kinases and cyclins. 882 17

Cell morphogenesis is a fundamental phenomenon that involves understanding a number of biological processes including the developmental program, polarity and cell division. Fission yeast sts5 mutant cells are round rather than cylindrical with cortical actin randomly dispersed. Genetic analyses demonstrate that the sts5+ gene is required for maintenance of cell shape during interphase when the cell normally exhibits polarised growth. The sts5 mutant is not defective in cell wall integrity. Deletion of ppe1+, which encodes a type 2A-like protein phosphatase, shows similar phenotypes to the sts5 mutant and these two mutations are synthetically lethal. Multicopy plasmids containing either the protein kinase C-like gene pck1+ or the protein tyrosine phosphatase pyp1+, an inhibitor of an osmosensing Sty1/Spc1 MAP-kinase, are capable of suppressing the sts5 mutation. Consistent with this, we have found that the wis1 mutation, which is defective in a MAP-kinase kinase of the pathway, suppresses the sts5 mutation. The predicted sts5+ gene product exhibits sequence similarity to two yeast proteins, Dis3 and Ssd1 and a nematode protein, F46E8.6, where the former two yeast proteins have been shown to be involved in cell cycle control and cell morphogenesis. The sts5+ gene is not essential for cell viability, but is absolutely required for polarised growth as the gene disruption showed the same phenotypes as those of the original mutants. Overexpression of the sts5+ gene resulted in altered cell morphology and, cortical actin in these overproducing cells was also abnormal, fainter and often dispersed. Anti-Sts5 antibody specifically detected a 130 kDa protein by western blotting. A green fluorescent protein-Sts5 fusion protein localised in the cytoplasm with a discrete punctate pattern, suggesting that the Sts5 protein is a component of a novel structure. These results have indicated that the Sts5 protein is a crucial determinant of polarised growth and that it functionally interacts with the serine/threonine phosphatase, protein kinase C, and an osmosensing MAP-kinase to maintain cell morphology.
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PMID:The fission yeast sts5+ gene is required for maintenance of growth polarity and functionally interacts with protein kinase C and an osmosensing MAP-kinase pathway. 888 83

The steroid/thyroid hormone receptor superfamily of ligand-activated transcription factors encompasses not only the receptors for steroids, thyroid hormone, retinoids and vitamin D, but also a large number of proteins whose functions and/or ligands are unknown and which are thus termed orphan receptors. Recent studies have highlighted the importance of phosphorylation in receptor function. Although most of the phosphorylation sites are serine and threonine residues, a few of the family members are also phosphorylated on tyrosine. Those steroid receptor family members that are bound to heat-shock proteins in the absence of ligand typically are basally phosphorylated and exhibit increases in phosphorylation upon ligand binding. Most of these sites contain Ser-Pro motifs, and there is evidence that cyclin-dependent kinases and MAP kinases (mitogen-activated protein kinases) phosphorylate subsets of these sites. In contrast, phosphorylation sites identified thus far in members of the family that bind to DNA in the absence of hormone typically do not contain Ser-Pro motifs and are frequently casein kinase II or protein kinase A sites. Phosphorylation has been implicated in DNA binding, transcriptional activation and stability of the receptors. The finding that some of the steroid receptor family members can be activated in the absence of ligand by growth factors or neurotransmitters that modulate kinase and/or phosphatase pathways underscores the role of phosphorylation in receptor function. Hence this family of transcription factors integrates signals from ligands as well as from signal transduction pathways, resulting in alterations in mRNA and protein expression that are unique to the complex signals received.
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PMID:Steroid hormone receptors and their regulation by phosphorylation. 892 Sep 64

MAP (mitogen-activated protein) kinases are activated by a family of dual specificity kinases called Meks (MAP kinase/Erk kinase). Mek1 can be activated by Raf by phosphorylation on serine 218 and serine 222. Mutation of these sites to acidic residues leads to constitutively active Mek1 in some cases. When fibroblast lines were infected with high titer retroviral stocks carrying these Mek1 genes, the resultant transformation and morphological changes correlated with the kinase activity of the respective Mek1 enzymes. Although [Asp218]- and [Asp218,Asp222]Mek immunoprecipitated from clonal cell lines could phosphorylate kinase-inactive Erk1 equally well in vitro, the endogenous MAP kinase activity was 5-7-fold greater in [Asp218]Mek1-infected clonal lines, and did not correlate with the degree of transformation. Analysis of the Erk1 pathway revealed Raf-1 activation, which correlated qualitatively with the MAP kinase activity seen in the [Asp218]- and [Asp218,Asp222]Mek1-infected clonal cell lines. Expression of dominant negative Ras did not affect the elevated Raf-1 activity observed in these cells, however. These data suggest that Mek1 phosphorylation site mutants activate Raf-1 and MAP kinase by a Ras-independent pathway and that the mechanism by which transformation occurs may utilize pathways that are MAP kinase-independent.
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PMID:Mek1 phosphorylation site mutants activate Raf-1 in NIH 3T3 cells. 894 Jan 80

Cytosolic phospholipase A2 is a constitutive and ubiquitous enzyme. Although its role in the early production of lipid mediators is well established, the mechanisms leading to its activation and its place in the signal transduction pathways triggered by G-protein-coupled receptors is still unclear. Two main mechanisms, have been involved in its activation: its translocation by the increase of intracellular calcium allowing access to its phospholipidic substrate, and its phosphorylation by serine/threonine protein kinases such as protein kinase C or MAP kinases. However these two mechanisms do not fully explain the activation of cytosolic phospholipase A2. The irreversible association to membranes observed after receptor stimulation suggests that a still unknown anchoring mechanism might be involved. The elucidation of this anchoring might take place in the overall synthesis of distinct lipid mediators pools able to play an intracellular role of second messengers or an extracellular role of autocrine/paracrine mediators.
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PMID:[Coupling of seven transmembrane domains receptors cytosolic PLA2: role of G proteins and protein kinases]. 895 92


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