Induction of cell shape changes through activation of the interleukin-3 common β chain receptor by the RON receptor-type tyrosine kinase

Akihiko Mera, Moritaka Suga, Masayuki Ando, Toshio Suda, Naoto Yamaguchi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The RON receptor-type tyrosine kinase, a member of the hepatocyte growth factor receptor family, is a receptor for macrophage-stimulating protein (MSP). Recently, we observed that MSP induces morphological changes in interleukin (IL)-3-dependent Ba/F3 cells ectopically expressing RON. We show here that stimulation of those cells with either MSP or IL-3 increases tyrosine phosphorylation of proteins of 130, 110, 90, 62, and 58 kDa and induces similar morphological changes, accompanied by unique nuclear shape and redistribution of F-actin. A tyrosine kinase inhibitor, genistein, blocked both the increase in tyrosine phosphorylation and morphological changes. Upon stimulation with either MSP or IL-3, prominent tyrosine- phosphorylated pp90 was similarly co-immunoprecipitated with the common β chain of IL-3 receptor (β(c)). Unlike IL-3, stimulation with MSP increased tyrosine phosphorylation of β(c) without activation of JAK2, resulting in morphological changes with modest cell growth. Confocal immunofluorescence analyses showed colocalization of RON, β(c), and tyrosine-phosphorylated proteins. In vitro kinase assays revealed that autophosphorylated RON phosphorylated β(c). These results suggest that the signaling pathway for morphological changes through β(c) and its associated protein pp90 is distinct from the pathway for cell growth in the IL-3 signal transduction system.

Original languageEnglish
Pages (from-to)15766-15774
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number22
DOIs
Publication statusPublished - 1999 May 28

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Cell Shape
Interleukin-3
Receptor Protein-Tyrosine Kinases
Chemical activation
Cells
Phosphorylation
Tyrosine
Cell growth
Interleukin-3 Receptors
Proto-Oncogene Proteins c-met
Signal transduction
Proteins
Genistein
Growth
Protein-Tyrosine Kinases
Fluorescent Antibody Technique
Actins
Assays
Signal Transduction
Phosphotransferases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Induction of cell shape changes through activation of the interleukin-3 common β chain receptor by the RON receptor-type tyrosine kinase. / Mera, Akihiko; Suga, Moritaka; Ando, Masayuki; Suda, Toshio; Yamaguchi, Naoto.

In: Journal of Biological Chemistry, Vol. 274, No. 22, 28.05.1999, p. 15766-15774.

Research output: Contribution to journalArticle

Mera, Akihiko ; Suga, Moritaka ; Ando, Masayuki ; Suda, Toshio ; Yamaguchi, Naoto. / Induction of cell shape changes through activation of the interleukin-3 common β chain receptor by the RON receptor-type tyrosine kinase. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 22. pp. 15766-15774.
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