tailieunhanh - Báo cáo khoa học: Role of extracellular signal regulated kinase 5 in neuronal survival

The newestmember of themitogenactivatedprotein (MAP) kinase family of proteins, extracellular signal regulated kinase 5 (ERK5; also known as big-mitogen activated kinase 1 or BMK1) is widely expressed in many tissues including the brain. Although growth factor activation of ERK5 innon-neuronal cells has been shown to contribute to cell proliferation, differentiation and transformation, until recently no information was available on the role of ERK5 in neuronalsurvival. Recent data suggests that ERK5 is activated by neurotrophic factors in primary neuronal cells and plays an important role in neurotrophin mediated neuronal survival. . | Eur. J. Biochem. 271 2056-2059 2004 FEBS 2004 doi MINIREVIEW Role of extracellular signal regulated kinase 5 in neuronal survival Jane E. Cavanaugh Department of Pharmacology University of Pittsburgh Pittsburgh PA USA The newest member of the mitogen activated protein MAP kinase family of proteins extracellular signal regulated kinase 5 ERK5 also known as big-mitogen activated kinase 1 or BMK1 is widely expressed in many tissues including the brain. Although growth factor activation of ERK5 in non-neuronal cells has been shown to contribute to cell proliferation differentiation and transformation until recently no information was available on the role of ERK5 in neuronal surivval. Recent data suggests that ERK5 is activated by neurotrophic factors in primary neuronal cells and plays an important role in neurotrophin mediated neuronal survival. These data also suggest that the mechanism of ERK5-mediated survival invvlvet a anscTÌ ilional regulation. Keywords Big-MAP kinase 1 BMK1 ERK5 MAP kinase neurons neuroprotection signal ttantdustíon urr-vival. ERK5 signaling The extracellular signal regulated kinase 5 ERK5 protein was simultaneously cloned by two groups in 1995. From these data it was noted that ERK5 shares sequence homology with ERK1 and ERK2 and contains a threonine and tyrosine TEY dual phosporylation motif similar to ERK1 2 1 2 . However a molecular mass of approximately 100 kDa a large C-terminus and unique 12 loop structure distinguish ERK5 from ERK1 2 and other members of the mitogen activated protein MAP kinase family. Upstream components of the ERK5 pathway include Ras MEKK2 MEKK3 MEK5 c-Src and Cot 1-7 . Downstream targets of the ERK5 pathway include myocyte enhancer factor 2C MEF2C MEF2A Sap1a and Ca 2 cAMP response element binding protein CREB 8-13 . Activation of ERK5 is reversed by dual-specificity phophatases C 100 and MAP kinase phosphatase 3 MKP3 which were previously thought to be specific for ERK1 2 10 . .