Cloning, chromosome localization, expression, and characterization of the ph-domain-contaiming grbir isoform Grb-IRPH/hGrb10γ

O. Pong, S. Farris, H. Y. Du, L. F. Kolakowski, L. J. Mandarine, J. Fan, F. Liu

    Research output: Contribution to journalArticle

    Abstract

    Grb-IR is SH2-domain-containing protein that binds with high affinity to the tyrosine phosphorylated insulin receptor (IR) and insulinlike growth factor-1 receptor (IGF-1R). At least two isoforms of Grb-IR, which differ in both the PH domain and the N-terminal region, have been identified in insulin target tissues such as human skeletal muscle. Here we report the cloning and characterization of the third Grb-IR isoform Grb-IRPH/hGrblOy. Grb-IRPH/hGrblOY cDNA was isolated from a human muscle cDNA library and mapped to chromosome 7. RNase protection assays and Western blot analysis showed that Grb-IR and Grb-IRPH are expressed differentially in human skeletal muscle, HeLa cells, and various breast cancer cell lines. Both isoforms interacted with the IR, IGF-1R and the Ret receptor in the yeast two-hybrid system and the interaction was significantly enhanced in the presence of an intact PH domain. Grb-IRPH also underwent insulin-stimulated serine phosphorylation which was blocked by PD98059, a specific inhibitor of mitogen-activated protein (MAP) kinase kinase (MEK), and wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. Taken together, our data suggest that Grb-IR isoforms are downstream signaling components of receptor tyrosine kinases including the IR, the IGF-1R, and the Ret receptor, and these isoforms may play different roles in signaling.

    Original languageEnglish (US)
    Pages (from-to)A919
    JournalFASEB Journal
    Volume11
    Issue number9
    StatePublished - Dec 1 1997

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

    Fingerprint Dive into the research topics of 'Cloning, chromosome localization, expression, and characterization of the ph-domain-contaiming grbir isoform Grb-IR<sup>PH</sup>/hGrb10γ'. Together they form a unique fingerprint.

  • Cite this

    Pong, O., Farris, S., Du, H. Y., Kolakowski, L. F., Mandarine, L. J., Fan, J., & Liu, F. (1997). Cloning, chromosome localization, expression, and characterization of the ph-domain-contaiming grbir isoform Grb-IRPH/hGrb10γ. FASEB Journal, 11(9), A919.