The MAP kinase cascade is essential for diverse signal transduction pathways.

Mitogen-activated protein (MAP) kinases are activated by combined tyrosine and threonine phosphorylation catalysed by MAP kinase kinase, a novel class of protein kinases with dual specificity for both tyrosine and serine/threonine. MAP kinase kinase is turned on by serine/threonine phosphorylation catalysed by an immediate upstream kinase. The MAP kinase cascade appears to be conserved during evolution and thus might play an essential role in diverse intracellular signaling processes from yeasts to vertebrates.

[1]  T. Sturgill,et al.  Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6. , 1991, Biochimica et biophysica acta.

[2]  T. Roberts,et al.  Raf-1 is a potential substrate for mitogen-activated protein kinase in vivo. , 1991, The Biochemical journal.

[3]  K. Nasmyth,et al.  Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1. , 1992, Genes & development.

[4]  Jonathan A. Cooper,et al.  Tyrosine phosphorylation and activation of homologous protein kinases during oocyte maturation and mitogenic activation of fibroblasts , 1991, Molecular and cellular biology.

[5]  E. Nishida,et al.  Mitogen-activated protein kinase and cytoskeleton in mitogenic signal transduction. , 1992, International review of cytology.

[6]  D. E. Levin,et al.  Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog , 1992, Molecular and cellular biology.

[7]  G. Nossal,et al.  The molecular and cellular basis of affinity maturation in the antibody response , 1992, Cell.

[8]  J. Shabanowitz,et al.  Identification of the regulatory phosphorylation sites in pp42/mitogen‐activated protein kinase (MAP kinase). , 1991, The EMBO journal.

[9]  Jonathan A. Cooper,et al.  Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes. , 1992, Science.

[10]  E. Nishida,et al.  Phosphorylation of Xenopus mitogen-activated protein (MAP) kinase kinase by MAP kinase kinase kinase and MAP kinase. , 1993, The Journal of biological chemistry.

[11]  A. Ashworth,et al.  The amino acid sequence of a mammalian MAP kinase kinase. , 1992, Oncogene.

[12]  E. Nishida,et al.  Xenopus MAP kinase activator is a serine/threonine/tyrosine kinase activated by threonine phosphorylation. , 1992, The EMBO journal.

[13]  T. Akiyama,et al.  Xenopus MAP kinase activator: identification and function as a key intermediate in the phosphorylation cascade. , 1992, The EMBO journal.

[14]  J. Gerhart,et al.  Cell cycle tyrosine phosphorylation of p34cdc2 and a microtubule-associated protein kinase homolog in Xenopus oocytes and eggs , 1991, Molecular and cellular biology.

[15]  A. Nasim,et al.  A gene which encodes a predicted protein kinase can restore some functions of the ras gene in fission yeast. , 1988, The EMBO journal.

[16]  C. Crews,et al.  The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. , 1992, Science.

[17]  P. Cohen,et al.  MAP kinase kinase from rabbit skeletal muscle A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone‐dependent signal transduction , 1992, FEBS letters.

[18]  Philip R. Cohen,et al.  MAP kinase activator from insulin‐stimulated skeletal muscle is a protein threonine/tyrosine kinase. , 1992, The EMBO journal.

[19]  B. Errede,et al.  STE11 is a protein kinase required for cell-type-specific transcription and signal transduction in yeast. , 1990, Genes & development.

[20]  P. Cohen,et al.  Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases , 1991, Nature.

[21]  E. Nishida,et al.  A mitogen-activated protein (MAP) kinase activating factor in mammalian mitogen-stimulated cells is homologous to Xenopus M phase MAP kinase activator. , 1992, The Journal of biological chemistry.

[22]  E. Krebs,et al.  Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases. , 1992, The Journal of biological chemistry.

[23]  P. Cohen,et al.  Activation of the MAP kinase pathway by the protein kinase raf , 1992, Cell.

[24]  S. Pelech,et al.  MAP kinases: charting the regulatory pathways. , 1992, Science.

[25]  P. Blackshear,et al.  Evidence that extracellular signal-regulated kinases are the insulin-activated Raf-1 kinase kinases. , 1992, The Journal of biological chemistry.

[26]  E. Krebs,et al.  Multiple components in an epidermal growth factor-stimulated protein kinase cascade. In vitro activation of a myelin basic protein/microtubule-associated protein 2 kinase. , 1991, The Journal of biological chemistry.

[27]  T. Toda,et al.  Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. , 1991, Genes & development.

[28]  E. Nishida,et al.  cDNA cloning of MAP kinase kinase reveals kinase cascade pathways in yeasts to vertebrates. , 1993, The EMBO journal.

[29]  Jonathan A. Cooper,et al.  Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. , 1992, The Journal of biological chemistry.

[30]  David L. Brautigan,et al.  Raf-1 activates MAP kinase-kinase , 1992, Nature.

[31]  E. Nishida,et al.  Activation of a Ca2+-inhibitable protein kinase that phosphorylates microtubule-associated protein 2 in vitro by growth factors, phorbol esters, and serum in quiescent cultured human fibroblasts. , 1988, The Journal of biological chemistry.

[32]  J. Maller,et al.  Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase , 1990, Nature.

[33]  T. Haystead,et al.  Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro. , 1992, Science.

[34]  E. Nishida,et al.  Activation of mitogen-activated protein kinase and its activator by ras in intact cells and in a cell-free system. , 1992, The Journal of biological chemistry.

[35]  E. Nishida,et al.  In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase , 1991, Nature.

[36]  M. Wigler,et al.  byr2, a Schizosaccharomyces pombe gene encoding a protein kinase capable of partial suppression of the ras1 mutant phenotype , 1991, Molecular and cellular biology.