Tyrosine Phosphorylation and Activation of Mitogen‐ Activated Protein Kinase in the Rat Brain Following Transient Cerebral Ischemia

Abstract: Activation of trophic factor receptors stimulates tyrosine phosphorylation on proteins and supports neuronal survival. We report that in the recovery phase following reversible cerebral ischemia, tyrosine phosphorylation increases in the membrane fraction of the resistant hippocampal CA3/dentate gyrus (DG) region, whereas in the sensitive CA1 region or striatum, tyrosine phosphorylation is less marked or decreases. In the cytosolic fractions, a 42‐kDa protein, identified as mitogen‐activated protein (MAP) kinase, is markedly phosphorylated and activated immediately following ischemia, in particular in CA3/DG, but not in striatum. In the CA1 region, phosphorylation of MAP kinase is less intense and decreases later during re‐ perfusion, which could explain the delay of neuronal degeneration in this structure. The data suggest that in ischemia‐resistant neurons the growth factor receptor‐coupled signaling cascade is stimulated and, through its effects on DNA transcription and mRNA translation, supports neuronal survival.

[1]  T. Wieloch,et al.  Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors , 1993, Journal of neurochemistry.

[2]  D. Warner Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat. , 1993 .

[3]  T. Wieloch,et al.  Casein Kinase II Activity in the Postischemic Rat Brain Increases in Brain Regions Resistant to Ischemia and Decreases in Vulnerable Areas , 1993, Journal of neurochemistry.

[4]  F Benfenati,et al.  Synaptic vesicle phosphoproteins and regulation of synaptic function. , 1993, Science.

[5]  T. Wieloch,et al.  Changes in tyrosine phosphorylation in neocortex following transient cerebral ischaemia. , 1993, NeuroReport.

[6]  E. Kandel,et al.  Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. , 1992, Science.

[7]  C. Creutz The annexins and exocytosis. , 1992, Science.

[8]  R. Campos-González,et al.  Tyrosine Phosphorylation of Microtubule‐Associated Protein Kinase After Transient Ischemia in the Gerbil Brain , 1992, Journal of neurochemistry.

[9]  J. Gurd,et al.  Depolarization‐Dependent Tyrosine Phosphorylation in Rat Brain Synaptosomes , 1992, Journal of neurochemistry.

[10]  A. Sharrocks,et al.  Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter , 1992, Nature.

[11]  E. Krebs,et al.  Identification of an Activator of the Microtubule‐Associated Protein 2 Kinases ERK1 and ERK2 in PC12 Cells Stimulated with Nerve Growth Factor or Bradykinin , 1992, Journal of neurochemistry.

[12]  K. Hossmann,et al.  Immunocytochemical Study of an Early Microglial Activation in Ischemia , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  S. Leevers,et al.  Activation of extracellular signal‐regulated kinase, ERK2, by p21ras oncoprotein. , 1992, The EMBO journal.

[14]  O. Lindvall,et al.  Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Volpe,et al.  In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia , 1991, Brain Research.

[16]  M. Cobb,et al.  ERKs, extracellular signal-regulated MAP-2 kinases. , 1991, Current opinion in cell biology.

[17]  R. Jope,et al.  Seizure‐Induced Protein Tyrosine Phosphorylation in Rat Brain Regions , 1991, Epilepsia.

[18]  V. Wheaton,et al.  Domains specifying thrombin–receptor interaction , 1991, Nature.

[19]  James R. Woodgett,et al.  Phosphorylation of c-jun mediated by MAP kinases , 1991, Nature.

[20]  E. Kandel,et al.  Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors , 1991, Nature.

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

[22]  D. Aunis,et al.  The participation of annexin II (calpactin I) in calcium-evoked exocytosis requires protein kinase C , 1991, The Journal of cell biology.

[23]  K. Takakura,et al.  Amelioration of delayed neuronal death in the hippocampus by nerve growth factor , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  L. Alberghina,et al.  Characterization of the tyrosine phosphorylation of calpactin I (annexin II) induced by platelet-derived growth factor. , 1991, The Biochemical journal.

[25]  M E Greenberg,et al.  Stimulation of protein tyrosine phosphorylation by NMDA receptor activation , 1991, Science.

[26]  R. Campos-González,et al.  Temperature-dependent tyrosine phosphorylation of microtubule-associated protein kinase in epidermal growth factor-stimulated human fibroblasts. , 1991, Cell regulation.

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

[28]  Nancy Y. Ip,et al.  ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF , 1991, Cell.

[29]  R. Erikson,et al.  Structure, expression, and regulation of protein kinases involved in the phosphorylation of ribosomal protein S6. , 1991, The Journal of biological chemistry.

[30]  K. Hossmann,et al.  [14C]Leucine Incorporation into Brain Proteins in Gerbils After Transient Ischemia: Relationship to Selective Vulnerability of Hippocampus , 1991, Journal of neurochemistry.

[31]  T. Hunter Cooperation between oncogenes , 1991, Cell.

[32]  L. Cantley,et al.  Oncogenes and signal transduction , 1991, Cell.

[33]  G. Thomas,et al.  MAP2 kinase and 70K S6 kinase lie on distinct signalling pathways , 1991, Nature.

[34]  E. Nielsen,et al.  2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. , 1990, Science.

[35]  P. Greengard,et al.  Synaptophysin and synapsin I as tools for the study of the exo-endocytotic cycle. , 1989, Cell biology international reports.

[36]  S. Kater,et al.  Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture , 1989, Journal of Neuroscience.

[37]  T. Wieloch,et al.  Postischemic Administration of Idazoxan, an α-2 Adrenergic Receptor Antagonist, Decreases Neuronal Damage in the Rat Brain , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[38]  S. Kater,et al.  Roles for mitotic history in the generation and degeneration of hippocampal neuroarchitecture , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[39]  B. Siesjö,et al.  Models for studying long‐term recovery following forebrain ischemia in the rat. 2. A 2‐vessel occlusion model , 1984, Acta neurologica Scandinavica.

[40]  Fred Plum,et al.  Temporal profile of neuronal damage in a model of transient forebrain ischemia , 1982, Annals of neurology.

[41]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[42]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[43]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. , 1992, Biotechnology.

[44]  G. Thomas,et al.  Intracellular messengers and the control of protein synthesis. , 1991, Pharmacology & therapeutics.

[45]  J. A. Traugh,et al.  Casein kinase I and II--multipotential serine protein kinases: structure, function, and regulation. , 1991, Advances in second messenger and phosphoprotein research.

[46]  U. Rapp Role of Raf-1 serine/threonine protein kinase in growth factor signal transduction. , 1991, Oncogene.

[47]  T. Hunter,et al.  Protein-tyrosine kinases. , 1985, Annual review of biochemistry.