Dimerization in MAP-kinase signaling.

The stimulus-dependent nuclear localization of the extracellular-signal- regulated kinases ERK1 and ERK2 is required for many of their actions, including induction of neurites in PC12 cells and transformation of fibroblasts. Phosphorylation of ERK2 causes it to form dimers, and the most flexible portions of the ERK2 molecule provide the surfaces for dimerization. It is thought that dimerization promotes nuclear localization of ERK2 by its effects on import, export or retention in cytoplasmic and nuclear compartments. Dimerization might also influence substrate interactions.

[1]  E. Nishida,et al.  Interaction of MAP kinase with MAP kinase kinase: its possible role in the control of nucleocytoplasmic transport of MAP kinase , 1997, The EMBO journal.

[2]  P. Cohen,et al.  EGF triggers neuronal differentiation of PC12 cells that overexpress the EGF receptor , 1994, Current Biology.

[3]  S. Green,et al.  PC12 cell neuronal differentiation is associated with prolonged p21ras activity and consequent prolonged ERK activity , 1992, Neuron.

[4]  J E Ferrell,et al.  The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. , 1998, Science.

[5]  T. Hunter,et al.  The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. , 1988, Science.

[6]  C. Marshall,et al.  Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation , 1995, Cell.

[7]  E. Nishida,et al.  Two co‐existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer , 1999, The EMBO journal.

[8]  E. Goldsmith,et al.  Phosphorylation of MAP Kinases by MAP/ERK Involves Multiple Regions of MAP Kinases* , 1999, The Journal of Biological Chemistry.

[9]  Arthur Weiss,et al.  Switching Signals On or Off by Receptor Dimerization , 1998, Cell.

[10]  E. Goldsmith,et al.  Phosphorylation of the MAP Kinase ERK2 Promotes Its Homodimerization and Nuclear Translocation , 1998, Cell.

[11]  E. Nishida,et al.  Cytoplasmic Localization of Mitogen-activated Protein Kinase Kinase Directed by Its NH2-terminal, Leucine-rich Short Amino Acid Sequence, Which Acts as a Nuclear Export Signal* , 1996, The Journal of Biological Chemistry.

[12]  J. Wilsbacher,et al.  The N-terminal ERK-binding Site of MEK1 Is Required for Efficient Feedback Phosphorylation by ERK2 in Vitro and ERK Activation in Vivo * , 1999, The Journal of Biological Chemistry.

[13]  E. Goldsmith,et al.  How MAP Kinases Are Regulated (*) , 1995, The Journal of Biological Chemistry.

[14]  Roger Y Tsien,et al.  Identification of a signal for rapid export of proteins from the nucleus , 1995, Cell.

[15]  Minoru Yoshida,et al.  CRM1 is responsible for intracellular transport mediated by the nuclear export signal , 1997, Nature.

[16]  E. Goldsmith,et al.  A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation , 1998, Current Biology.

[17]  E. Goldsmith,et al.  The structure of mitogen-activated protein kinase p38 at 2.1-A resolution. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Elion,et al.  Nuclear Shuttling of Yeast Scaffold Ste5 Is Required for Its Recruitment to the Plasma Membrane and Activation of the Mating MAPK Cascade , 1999, Cell.

[19]  A. Brunet,et al.  Growth Factor–induced p42/p44 MAPK Nuclear Translocation and Retention Requires Both MAPK Activation and Neosynthesis of Nuclear Anchoring Proteins , 1998, The Journal of cell biology.

[20]  T. Clackson,et al.  A hot spot of binding energy in a hormone-receptor interface , 1995, Science.

[21]  A. Brunet,et al.  Nuclear translocation of p42/p44 mitogen‐activated protein kinase is required for growth factor‐induced gene expression and cell cycle entry , 1999, The EMBO journal.

[22]  E. Goldsmith,et al.  Autophosphorylation activates the soluble cytoplasmic domain of the insulin receptor in an intermolecular reaction. , 1989, The Journal of biological chemistry.

[23]  Elizabeth J. Goldsmith,et al.  Activation Mechanism of the MAP Kinase ERK2 by Dual Phosphorylation , 1997, Cell.

[24]  Masahiko Hibi,et al.  c-Jun Can Recruit JNK to Phosphorylate Dimerization Partners via Specific Docking Interactions , 1996, Cell.

[25]  N. Osheroff,et al.  Extracellular Signal-Regulated Kinase Activates Topoisomerase IIα through a Mechanism Independent of Phosphorylation , 1999, Molecular and Cellular Biology.

[26]  Paul R. Caron,et al.  Crystal Structure of p38 Mitogen-activated Protein Kinase* , 1996, The Journal of Biological Chemistry.

[27]  P. Caron,et al.  Crystal structure of JNK3: a kinase implicated in neuronal apoptosis. , 1998, Structure.

[28]  Elizabeth J. Goldsmith,et al.  Atomic structure of the MAP kinase ERK2 at 2.3 Å resolution , 1994, Nature.