Disease specificity of kinase domains: The src-encoded catalytic domain converts erbB into a sarcoma oncogene

Chi Ming Chang, Hui Kuo G. Shu, Hsing Jien Kung

研究成果: 雜誌貢獻文章

6 引文 斯高帕斯(Scopus)

摘要

src and erbB are two tyrosine kinase-encoding oncogenes carried by retroviruses, which have distinct disease specificities. The former induces predominantly sarcomas, and the latter, leukemias. Src and ErbB have similar catalytic domains but have very different regulatory domains. A wealth of information exists concerning how different regulatory domains [Src homology 2 (SH2) and SH3 domains and autophosphorylation sites] control substrate and disease specificities. Whether the catalytic domain helps determine these specificities remains to be explored. Here we show that the Src catalytic domain is enzymatically active when substituted into the ErbB backbone and interacts with the ErbB regulatory domain. This ErbB/Src chimera displays autophosphorylation and substrate phosphorylation patterns different from those of both Src and ErbB. Neither SH2 and SH3 nor autophosphorylation sites are required for the Src catalytic domain to exert its fibroblast transforming ability. Most significantly, the catalytic domain can convert erbB from a leukemogenic oncogene into a sarcomagenic oncogene, suggesting that the leukemogenic determinants in part reside within the ErbB catalytic domain.
原文英語
頁(從 - 到)3928-3932
頁數5
期刊Proceedings of the National Academy of Sciences of the United States of America
92
發行號9
DOIs
出版狀態已發佈 - 四月 25 1995
對外發佈Yes

ASJC Scopus subject areas

  • General

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