scholarly journals Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage ofPlasmodium falciparumAsexual Maturation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Farah Aida Dahalan ◽  
Hasidah Mohd Sidek ◽  
Mogana Das Murtey ◽  
Mohammed Noor Embi ◽  
Jamaiah Ibrahim ◽  
...  
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
Inflammatory Responses ◽  
Kinase Activation ◽  
Ring Form ◽  
Phosphorylated Form ◽  
Promising Target ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
First Time

Plasmodium falciparummitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that theP. falciparumspecific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages ofP. falciparumand is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites’ developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.

scholarly journals Selective activation of p42 mitogen-activated protein (MAP) kinase in murine B lymphoma cell lines by membrane immunoglobulin cross-linking. Evidence for protein kinase C-independent and -dependent mechanisms of activation

1992 ◽  
Vol 287 (1) ◽  
pp. 269-276 ◽  
Author(s):  
M R Gold ◽  
J S Sanghera ◽  
J Stewart ◽  
S L Pelech
Keyword(s):  
Map Kinase ◽  
Tyrosine Phosphorylation ◽  
Cell Lines ◽  
Map Kinases ◽  
Phorbol Esters ◽  
Cross Linking ◽  
Kinase Activation ◽  
Membrane Immunoglobulin ◽  
Protein Map ◽  
Mitogen Activated Protein

Cross-linking of membrane immunoglobulin (mIg), the B lymphocyte antigen receptor, with anti-receptor antibodies stimulates tyrosine phosphorylation of a number of proteins, including one of 42 kDa. Proteins with a similar molecular mass are tyrosine-phosphorylated in response to receptor stimulation in other cell types and have been identified as serine/threonine kinases, termed mitogen-activated protein (MAP) kinases or extracellular signal-regulated kinases (ERKs). The MAP kinases constitute a family of related kinases, at least three of which have molecular masses of 40-45 kDa. In this paper we show that mIg cross-linking stimulated the myelin basic protein phosphotransferase activity characteristic of MAP kinase in both mature and immature murine B cell lines. This enzyme activity co-purified on three different columns with a 42 kDa protein that was tyrosine-phosphorylated (pp42) in response to mIg cross-linking and which reacted with a panel of anti-(MAP kinase) antibodies. Although immunoblotting with the anti-(MAP kinase) antibodies showed that these B cell lines expressed both 42 kDa and 44 kDa forms of MAP kinase, only the 42 kDa form was activated and tyrosine-phosphorylated to a significant extent. Activation of protein kinase C (PKC) with phorbol esters also resulted in selective tyrosine phosphorylation and activation of the 42 kDa MAP kinase. This suggested that mIg-induced MAP kinase activation could be due to stimulation of PKC by mIg. However, mIg-stimulated MAP kinase activation and pp42 tyrosine phosphorylation was only partially blocked by a PKC inhibitor, the staurosporine analogue Compound 3. In contrast, Compound 3 completely blocked the ability of phorbol esters to stimulate MAP kinase activity and induce tyrosine phosphorylation of pp42. Thus mIg may activate MAP kinase by both PKC-dependent and -independent mechanisms.

cAMP inhibits mitogen-activated protein (MAP) kinase activation and resumption of meiosis, but exerts no effects after spontaneous germinal vesicle breakdown (GVBD) in mouse oocytes

1999 ◽  
Vol 11 (2) ◽  
pp. 81 ◽  
Author(s):  
Q. Y. Sun ◽  
Q. Lu ◽  
H. Breitbart ◽  
D. Y. Chen
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
Specific Inhibitor ◽  
Germinal Vesicle ◽  
Germinal Vesicle Breakdown ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Kinase Phosphorylation ◽  
Pkc Activation

Various signaling molecules have been implicated in the oocyte G2/MII transition, including protein kinase C (PKC), cAMP and mitogen-activated protein (MAP) kinases. However, the cross-talk among these signaling pathways has not been elucidated. The present study demonstrates that both germinal vesicle break down (GVBD) and MAP kinase phosphorylation (activation) are inhibited when intraoocyte cAMP is increased by treating the GV-intact oocytes with dibutyryl cyclic AMP (dbcAMP), forskolin, or isobutylmethylxanthine (IBMX). Okadaic acid, a specific inhibitor of protein phosphatase-1 and -2A, completely overcame this effect. Calphostin C, a specific inhibitor of PKC, accelerated both GVBD and MAP kinase phosphorylation, and this effect was attenuated by increased intraoocyte cAMP, whereas PKC activation inhibited these events. Once GVBD occurred, the progression of oocyte maturation and MAP kinase phosphorylation were independent of cAMP. These results indicate that an increase in intraoocyte cAMP, in synergy with PKC activation, initiates a cascade of events resulting in inhibition of MAP kinase phosphorylation and GVBD in the mouse oocyte.

scholarly journals Novel members of the mitogen-activated protein kinase activator family in Xenopus laevis

1993 ◽  
Vol 13 (9) ◽  
pp. 5738-5748
Author(s):  
B M Yashar ◽  
C Kelley ◽  
K Yee ◽  
B Errede ◽  
L I Zon
Keyword(s):  
Protein Kinase ◽  
Xenopus Laevis ◽  
Map Kinase ◽  
Protein Kinases ◽  
Map Kinases ◽  
Yeast Cells ◽  
Amino Acid Sequence Similarity ◽  
Kinase Activation ◽  
Mitogen Activated Protein ◽  
Activation Pathways

Mitogen-activated protein (MAP) kinases comprise an evolutionarily conserved family of proteins that includes at least three vertebrate protein kinases (p42, p44, and p55 MAPK) and five yeast protein kinases (SPK1, MPK1, HOG1, FUS3, and KSS1). Members of this family are activated by a variety of extracellular agents that influence cellular proliferation and differentiation. In Saccharomyces cerevisiae, there are multiple physiologically distinct MAP kinase activation pathways composed of structurally related kinases. The recently cloned vertebrate MAP kinase activators are structurally related to MAP kinase activators in these yeast pathways. These similarities suggest that homologous kinase cascades are utilized for signal transduction in many, if not all, eukaryotes. We have identified additional members of the MAP kinase activator family in Xenopus laevis by a polymerase chain reaction-based analysis of embryonic cDNAs. One of the clones identified (XMEK2) encodes a unique predicted protein kinase that is similar to the previously reported activator (MAPKK) in X. laevis. XMEK2, a highly expressed maternal mRNA, is developmentally regulated during embryogenesis and expressed in brain and muscle. Expression of XMEK2 in yeast cells suppressed the growth defect associated with loss of the yeast MAP kinase activator homologs, MKK1 and MKK2. Partial sequence of a second cDNA clone (XMEK3) identified yet another potential MAP kinase activator. The pattern of expression of XMEK3 is distinct from that of p42 MAPK and XMEK2. The high degree of amino acid sequence similarity of XMEK2, XMEK3, and MAPKK suggests that these three are related members of an amphibian family of protein kinases involved in the activation of MAP kinase. Discovery of this family suggests that multiple MAP kinase activation pathways similar to those in yeast cells exist in vertebrates.

scholarly journals Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1

1998 ◽  
Vol 330 (2) ◽  
pp. 605-609 ◽  
Author(s):  
C. M. Gerben ZONDAG ◽  
R. Friso POSTMA ◽  
Ingrid VAN ETTEN ◽  
Ingrid VERLAAN ◽  
H. Wouter MOOLENAAR
Keyword(s):  
Adenylate Cyclase ◽  
Map Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Lpa Receptor ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are structurally related lipid mediators that act on distinct G-protein-coupled receptors to evoke similar responses, including Ca2+ mobilization, adenylate cyclase inhibition, and mitogen-activated protein (MAP) kinase activation. However, little is still known about the respective receptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is similar to an orphan Gi-coupled receptor termed Edg-1. Here we show that expression of Edg-1 in Sf9 and COS-7 cells results in inhibition of adenylate cyclase and activation of MAP kinase (Gi-mediated), but not Ca2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 cannot substitute for Edg-1. Thus the Edg-1 receptor is capable of mediating a subset of the cellular responses to S1P.

scholarly journals Novel members of the mitogen-activated protein kinase activator family in Xenopus laevis.

1993 ◽  
Vol 13 (9) ◽  
pp. 5738-5748 ◽  
Author(s):  
B M Yashar ◽  
C Kelley ◽  
K Yee ◽  
B Errede ◽  
L I Zon
Keyword(s):  
Protein Kinase ◽  
Xenopus Laevis ◽  
Map Kinase ◽  
Protein Kinases ◽  
Map Kinases ◽  
Yeast Cells ◽  
Amino Acid Sequence Similarity ◽  
Kinase Activation ◽  
Mitogen Activated Protein ◽  
Activation Pathways

Mitogen-activated protein (MAP) kinases comprise an evolutionarily conserved family of proteins that includes at least three vertebrate protein kinases (p42, p44, and p55 MAPK) and five yeast protein kinases (SPK1, MPK1, HOG1, FUS3, and KSS1). Members of this family are activated by a variety of extracellular agents that influence cellular proliferation and differentiation. In Saccharomyces cerevisiae, there are multiple physiologically distinct MAP kinase activation pathways composed of structurally related kinases. The recently cloned vertebrate MAP kinase activators are structurally related to MAP kinase activators in these yeast pathways. These similarities suggest that homologous kinase cascades are utilized for signal transduction in many, if not all, eukaryotes. We have identified additional members of the MAP kinase activator family in Xenopus laevis by a polymerase chain reaction-based analysis of embryonic cDNAs. One of the clones identified (XMEK2) encodes a unique predicted protein kinase that is similar to the previously reported activator (MAPKK) in X. laevis. XMEK2, a highly expressed maternal mRNA, is developmentally regulated during embryogenesis and expressed in brain and muscle. Expression of XMEK2 in yeast cells suppressed the growth defect associated with loss of the yeast MAP kinase activator homologs, MKK1 and MKK2. Partial sequence of a second cDNA clone (XMEK3) identified yet another potential MAP kinase activator. The pattern of expression of XMEK3 is distinct from that of p42 MAPK and XMEK2. The high degree of amino acid sequence similarity of XMEK2, XMEK3, and MAPKK suggests that these three are related members of an amphibian family of protein kinases involved in the activation of MAP kinase. Discovery of this family suggests that multiple MAP kinase activation pathways similar to those in yeast cells exist in vertebrates.

scholarly journals BWMK1, a Novel MAP Kinase Induced by Fungal Infection and Mechanical Wounding in Rice

1999 ◽  
Vol 12 (12) ◽  
pp. 1064-1073 ◽  
Author(s):  
Chaozu He ◽  
Steven Haw Tien Fong ◽  
Daichang Yang ◽  
Guo-Liang Wang
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
Magnaporthe Grisea ◽  
Mechanical Wounding ◽  
C Terminus ◽  
Acid Protein ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Rice Leaves ◽  
Activation Motif

The activation of the mitogen-activated protein (MAP) kinases by different environmental stresses has been previously observed in several dicot plant species. Here, we report the isolation of a novel MAP kinase in rice that is induced during infection by the blast fungus Magnaporthe grisea or upon mechanical wounding. The gene is designated as BWMK1 for blast- and wound-induced MAP kinase. The cDNA of BWMK1 was isolated from rice leaves challenged by the blast pathogen. Transcripts of the corresponding gene accumulated in rice leaves 4 h after blast inoculation and 30 min after mechanical wounding. This gene encodes a 506 amino acid protein that contains a new dual-phosphorylation activation motif TDY and about 150 unique amino acids on its C terminus. In-gel kinase activity and immunoprecipitation assays confirmed that BWMK1 is a functional MAP kinase. These results show that BWMK1 is a new member of the plant MAP kinase family and may mediate both defense and wound signaling in rice.

Signaling through JAM-1 and αvβ3 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and αvβ3 complex

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2108-2114 ◽  
Author(s):  
Meghna U. Naik ◽  
Shaker A. Mousa ◽  
Charles A. Parkos ◽  
Ulhas P. Naik
Keyword(s):  
Endothelial Cell ◽  
Growth Factor ◽  
Map Kinase ◽  
Integrin Αvβ3 ◽  
Tube Formation ◽  
Cell Junctions ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Multistep Process

Abstract Growth factor–induced neovascularization has received a great deal of attention because it is fundamental to the growth and metastasis of solid tumors. This multistep process requires extensive signaling through growth factor receptors and integrins. Among the integrins involved in this process, integrin αvβ3 is specific to basic fibroblast growth factor (bFGF)–induced angiogenesis. Here we show that junctional adhesion molecule 1/A (JAM-1/A) and αvβ3 form a complex in the absence of bFGF. JAM-1, which is normally localized at the cell-cell junctions of quiescent endothelial cells, redistributes to the cell surface on bFGF treatment. Blockage of the extracellular domain of JAM-1 inhibits bFGF-induced endothelial cell morphology, proliferation, and angiogenesis. Additionally, mutation in the JAM-1 cytoplasmic domain blocks bFGF-induced mitogen-activated protein (MAP) kinase activation and ablates its ability to induce endothelial cell tube formation, suggesting that signaling through JAM-1 is key to bFGF-induced signaling. Immunoprecipitation analysis suggests that bFGF signaling dissociates the JAM-1/ αvβ3 complex, allowing for signaling through JAM-1 and αvβ3. In addition, blockage of either JAM-1 or αvβ3 inhibits bFGF-induced MAP kinase activation. Thus, our results suggest that signaling through JAM-1 and αvβ3 is necessary for bFGF-induced angiogenesis.

scholarly journals c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases.

1994 ◽  
Vol 14 (10) ◽  
pp. 6683-6688 ◽  
Author(s):  
A Minden ◽  
A Lin ◽  
T Smeal ◽  
B Dérijard ◽  
M Cobb ◽  
...  
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
New Members ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Extracellular Stimuli ◽  
Terminal Site ◽  
Stimulation Of

c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli, including growth factors, cytokines, and UV irradiation. New members of the mitogen-activated protein (MAP) kinase group of signal-transducing enzymes, termed JNKs, bind to the activation domain of c-Jun and specifically phosphorylate these sites. However, the N-terminal sites of c-Jun were also suggested to be phosphorylated by two other MAP kinases, ERK1 and ERK2. Despite these reports, we find that unlike the JNKs, ERK1 and ERK2 do not phosphorylate the N-terminal sites of c-Jun in vitro; instead they phosphorylate an inhibitory C-terminal site. Furthermore, the phosphorylation of c-Jun in vivo at the N-terminal sites correlates with activation of the JNKs but not the ERKs. The ERKs are probably involved in the induction of c-fos expression and thereby contribute to the stimulation of AP-1 activity. Our study suggests that two different branches of the MAP kinase group are involved in the stimulation of AP-1 activity through two different mechanisms.

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