Association of the proto‐oncogene product Dbl with G protein βγ subunits

FEBS Letters

Kaziro, Yoshito¹  Satoh, Takaya¹  Nishida, Kazuhiko¹ 

[1] Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

关键词: Cdc42;    Dbl;    G protein βγ subunit;    Guanine nucleotide exchange factor;    Rac;    Rho;    DH;    Dbl homology;    Gα;    G protein α subunit;    Gβγ;    G protein βγ subunits;    GEF;    guanine nucleotide exchange factor;    GST;    glutathione S-transferase;    HA;    hemagglutinin;    HEK;    human embryonic kidney;    JNK;    c-Jun N-terminal kinase;    PCR;    polymerase chain reaction;    PH;    pleckstrin homology;   

DOI  :  10.1016/S0014-5793(99)01244-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. Its activity is directed by intracellular signals mediated by various types of receptors such as G protein-coupled receptors. However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. Here, we show the association of Dbl with G protein βγ subunits (Gβγ) in transient co-expression and cell-free systems. An amino-terminal portion conserved among a subset of Dbl family proteins is sufficient for the binding of Gβγ. In fact, Ost and Kalirin, which contain this Gβγ-binding motif, also associate with Gβγ. c-Jun N-terminal kinase was synergistically activated upon co-expression of Dbl and Gβ in a dominant-negative Rho-sensitive manner. However, GEF activity of Dbl toward Rho as measured by in vitro GDP binding assays remained unaffected following Gβγ binding, suggesting that additional signals may be required for the regulation of Dbl.

【 授权许可】

Unknown