XCL100, an inducible nuclear MAP kinase phosphatase from Xenopus laevis: its role in MAP kinase inactivation in differentiated cells and its expression during early development

T Lewis, L A Groom, A A Sneddon, C Smythe, S M Keyse

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31 Citations (Scopus)

Abstract

We have cloned the Xenopus laevis homologue (XCL100) of the human CL100 (Thr/Tyr) MAP kinase phosphatase. Expression of the XCL100 mRNA and protein is inducible by serum stimulation and oxidative/heat stress in a X. laevis kidney cell line. In contrast, XCL100 is constitutively expressed in growing Xenopus oocytes. Recombinant XCL100 protein is able to dephosphorylate both tyrosine and threonine residues of activated p42 MAP kinase in vitro and both the Xenopus and human CL100 proteins were localised predominantly in the nucleus in transfected COS-1 cells. As nuclear translocation of activated MAP kinase is necessary for some of its essential functions in proliferation and cell differentiation our results indicate a role for CL100 in the regulation of these nuclear signalling events. In Xenopus kidney cells both heat shock and serum stimulation lead to transient activation of MAP kinase. However, in contrast to results previously reported from studies on mammalian fibroblasts the inactivation of MAP kinase in these epitheloid cells is rapid and is not dependent on synthesis of new protein. These results indicate that the induction of CL100 (or CL100-like enzymes) may not be required for MAP kinase inactivation in all cell types. Finally, during early embryogenesis, levels of XCL100 mRNA are greatly increased at the mid-blastula transition, suggesting that this enzyme may be involved in the regulation of MAP kinase activity during early development.
Original languageEnglish
Pages (from-to)2885-96
Number of pages12
JournalJournal of Cell Science
Volume108 ( Pt 8)
Publication statusPublished - 1995

Keywords

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cloning, Molecular
  • DNA Primers
  • Dual Specificity Phosphatase 1
  • Embryo, Nonmammalian
  • Enzyme Activation
  • Enzyme Induction
  • Female
  • Humans
  • Immediate-Early Proteins
  • Kidney
  • Kinetics
  • Mitogen-Activated Protein Kinase Phosphatases
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatases
  • Rabbits
  • Recombinant Proteins
  • Reticulocytes
  • Sequence Homology, Amino Acid
  • Xenopus Proteins
  • Xenopus laevis

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