v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-03-29

AUTHORS

Kazuya Machida, Satoru Matsuda, Kenichi Yamaki, Takeshi Senga, Aye Aye Thant, Hisashi Kurata, Kou Miyazaki, Kazuhiko Hayashi, Takahito Okuda, Toshio Kitamura, Tetsuo Hayakawa, Michinari Hamaguchi

ABSTRACT

We investigated the effect of cell transformation by v-src on the expression and tyrosine phosphorylation of SHPS-1, a putative docking protein for SHP-1 and SHP-2. We found that transformation by v-src virtually inhibited the SHPS-1 expression at mRNA level. While nontransforming Src kinases including c-Src, nonmyristoylated forms of v-Src had no inhibitory effect on SHPS-1 expression, transforming Src kinases including wild-type v-Src and chimeric mutant of c-Src bearing v-Src SH3 substantially suppressed the SHPS-1 expression. In cells expressing temperature sensitive mutant of v-Src, suppression of the SHPS-1 expression was temperature-dependent. In contrast, tyrosine phosphorylation of SHPS-1 was rather activated in cells expressing c-Src or nonmyristoylated forms of v-Src. SHPS-1 expression in SR3Y1 was restored by treatment with herbimycin A, a potent inhibitor of tyrosine kinase, or by the expression of dominant negative form of Ras. Contrary, active form of Mek1 markedly suppressed SHPS-1 expression. Finally, overexpression of SHPS-1 in SR3Y1 led to the drastic reduction of anchorage independent growth of the cells. Taken together, our results suggest that the suppression of SHPS-1 expression is a pivotal event for cell transformation by v-src, and the Ras-MAP kinase cascade plays a critical role in the suppression. More... »

PAGES

1710-1718

Journal

TITLE

Oncogene

ISSUE

13

VOLUME

19

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1203497

DOI

http://dx.doi.org/10.1038/sj.onc.1203497

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049814739

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10763828


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382 Department of Internal Medicine III, Nagoya University School of Medicine, 65 Tsurumai-cho, 466-8550, Showa-ku, Nagoya, Japan
383 Department of Molecular Pathogenesis, Nagoya University of School of Medicine, 65 Tsurumai-cho, 466-8550, Showa-ku, Nagoya, Japan
384 Department of Surgery I, Nagoya University School of Medicine, 65 Tsurumai-cho, 466-8550, Showa-ku, Nagoya, Japan
385 rdf:type schema:Organization
 




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