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 language | English |
|---|---|
| Pages (from-to) | 15766-15774 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 274 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 1999 May 28 |
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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 journal › Article
}
TY - JOUR
T1 - Induction of cell shape changes through activation of the interleukin-3 common β chain receptor by the RON receptor-type tyrosine kinase
AU - Mera, Akihiko
AU - Suga, Moritaka
AU - Ando, Masayuki
AU - Suda, Toshio
AU - Yamaguchi, Naoto
PY - 1999/5/28
Y1 - 1999/5/28
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033060256&partnerID=8YFLogxK
U2 - 10.1074/jbc.274.22.15766
DO - 10.1074/jbc.274.22.15766
M3 - Article
C2 - 10336478
AN - SCOPUS:0033060256
VL - 274
SP - 15766
EP - 15774
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -