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NOTE: This Newsletter will be moved to the PFPC “Members” section starting January 1, 2005. |
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MAPK MAPK stands for Mitogen-Activated-Protein-Kinase. MAPKs are important signal transducing enzymes that are involved in many facets of cellular regulation (Gudermann et al, 2000; Chang et al, 2001; Davis, 1995). It is an important mechanism to transduce "mitogenic signals" from the cell membrane to the nucleus (Gudermann et al, 2000; Davis, 1995). MAPK is a low abundance serine--threonine protein kinase, transiently activated in many cell types by a variety of "mitogens", including insulin, epidermal growth factor, phorbol esters, antigens, etc. and fluoride [potentiated by mere presence of Al]. While initial research concentrated on defining the components and organization of MAPK signalling cascades, recent studies have begun to shed light on the physiological functions of these cascades in the control of gene expression, cell proliferation and programmed cell death (Chang et al, 2001). "Crosstalk" phenomena with ras have been established (Seo et al, 2000;Misra et al, 2000). MAPK 42 and MAPK 44 are also called ERK1 and ERK2, which means Extracellular-Regulated-Kinase 1 and 2, respectively. MAPK 42 is thought to be of a molecular weight of 42 kDa, while MAPK 44 is of 44 kDa. MAPK pathways promote cellular proliferation by activating critical steps in the intracellular transduction of survival signals (Schwindiger, 2001). These pathways have profound effects on the pathology of thyroid disease, chronic inflammation, heart disease, stroke, diabetes mellitus, Alzheimer's Disease, autism, cancer etc. The role of MAPK is crucial in embryonic development. In the past the MAPK signalling pathway was viewed as distinct from the G protein-activated pathway. However, research conducted during the last 10 years has brought abundant evidence that the MAPK pathway is activated by G/11. The MAPK pathway is thought to be activated by elevated Ca(2+), which triggers the p21(ras)-dependent MAPK signaling cascade (Mizra et al, 2000). Gq/11 have been unequivocally established to be the transducing G proteins for Ca(2+)-mobilizing receptors (Taylor & Exton, 1991; Exton, 1993; Obukhov et al, 1996; Schaefer et al, 2000). If G q/11 activates MAPK, it is clear that over-expression of G q/11 will lead to numerous diseases. REFERENCES: Blaukat A, Barac A, Cross MJ, Offermanns S, Dikic I - "G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Galpha(q) and Galpha(i) signals"Mol Cell Biol 20(18):6837-48 (2000) Chang L, Karin M - "Mammalian MAP kinase signalling cascades" Nature 410(6824):37-40 (2001) Exton JH - "Role of G proteins in activation of phosphoinositide phospholipase C" Adv Second Messenger Phosphoprotein Res 28:65-72 (1993) Gudermann T, Grosse R, Schultz G - "Contribution of receptor/G protein signaling to cell growth and Kyriakis JM, Avruch J - "Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation" Physiol Rev 81(2):807-69 (2001) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 11274345&form=6&db=m&Dopt=r Misra UK, Gawdi G, Pizzo SV - "Beryllium fluoride-induced cell proliferation: a process requiring P21(ras)-dependent activated signal transduction and NF-kappaB-dependent gene regulation" J Leukoc Biol 71(3):487-94 (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 11867686&form=6&db=m&Dopt=r Obukhov AG, Harteneck C, Zobel A, Harhammer R, Kalkbrenner F, Leopoldt D, Luckhoff A, Nurnberg B, Schultz G - "Direct activation of trpl cation channels by G alpha11 subunits" EMBO J 15(21):5833-8 (1996) Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G - "Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5" J Biol Chem 275(23):17517-26 (2000) Schwindinger WF, Robishaw JD - "Heterotrimeric G-protein betagamma-dimers in growth and differentiation" Oncogene 20(13):1653-60 (2001) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 11313913&form=6&db=m&Dopt=r Seo B, Choy EW, Maudsley S, Miller WE, Wilson BA, Luttrell LM - "Pasteurella multocida toxin stimulates mitogen-activated protein kinase via G(q/11)-dependent transactivation of the epidermal growth factor receptor" Biol Chem 275(3):2239-45 (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 10636931&form=6&db=m&Dopt=r Taylor SJ, Exton JH - "Two alpha subunits of the Gq class of G proteins stimulate phosphoinositide phospholipase C-beta 1 activity" FEBS Lett 286(1-2):214-6 (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid= 1650713&form=6&db=m&Dopt=r Wu PS, Moriscot AS, Knowlton KU, Hilal-Dandan R, He H, Dillmann WH-"Alpha 1-adrenergic stimulation inhibits 3,5,3'-triiodothyronine-induced expression of the rat heart sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene." Endocrinology 138(1):114-20 (1997) Yan Y, Chi PP, Bourne HR - "RGS4 inhibits Gq-mediated activation of mitogen-activated protein kinase and phosphoinositide synthesis."J Biol Chem 272(18):11924-7 (1997)
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