MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway

Jei Liang Lin, Hua Chien Chen, Hsin I. Fang, Dan Robinson, Hsing Jien Kung, Hsiu Ming Shih

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

In this study, we report the cloning and characterization of a novel human Ste20-related kinase that we designated MST4 (accession number AF231012). The 416 amino acid full-length MST4 contains an amino-terminal kinase domain, which is highly homologous to MST3 and SOK, and a unique carboxy-terminal domain. Northern blot analysis indicated that MST4 is highly expressed in placenta, thymus, and peripheral blood leukocytes. Wild-type but not kinase-dead MST4 can phosphorylate myelin basic protein in an in vitro kinase assay. MST4 specifically activates ERK but not JNK or p38 MAPK in transient transfected cells or in stable cell lines. Overexpression of dominant negative MEK1 or treatment with PD98059 abolishes MST4-induced ERK activity, whereas dominant-negative Ras or c-Raf-1 mutants failed to do so, indicating MST4 activates MEK1/ERK via a Ras/Raf-1 independent pathway. HeLa and Phoenix cell lines overexpressing wild-type, but not kinase-dead, MST4 exhibit increased growth rate and form aggressive soft-agar colonies. These phenotypes can be inhibited by PD98059. These results provide the first evidence that MST4 is biologically active in the activation of MEK/ERK pathway and in mediating cell growth and transformation.

Original languageEnglish
Pages (from-to)6559-6569
Number of pages11
JournalOncogene
Volume20
Issue number45
DOIs
Publication statusPublished - Oct 4 2001
Externally publishedYes

Fingerprint

MAP Kinase Signaling System
Phosphotransferases
Growth
Cell Line
Myelin Basic Protein
p38 Mitogen-Activated Protein Kinases
HeLa Cells
Northern Blotting
Thymus Gland
Placenta
Agar
Organism Cloning
Leukocytes
Phenotype
Amino Acids
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Keywords

  • Cell transformation
  • Kinase signaling
  • Ste20 kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. / Lin, Jei Liang; Chen, Hua Chien; Fang, Hsin I.; Robinson, Dan; Kung, Hsing Jien; Shih, Hsiu Ming.

In: Oncogene, Vol. 20, No. 45, 04.10.2001, p. 6559-6569.

Research output: Contribution to journalArticle

Lin, Jei Liang ; Chen, Hua Chien ; Fang, Hsin I. ; Robinson, Dan ; Kung, Hsing Jien ; Shih, Hsiu Ming. / MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. In: Oncogene. 2001 ; Vol. 20, No. 45. pp. 6559-6569.
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