Mutation of an N‐terminal acidic‐rich region of p115‐RhoGEF dissociates α13 binding and α13‐promoted plasma membrane recruitment

FEBS Letters

Bhattacharyya, Raja¹  Wedegaertner, Philip B¹ 

[1] Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th St., 839 BLSB, Philadelphia, PA 19107, USA

关键词: Heterotrimeric guanine nucleotide binding protein;    Ras homology GTPase;    Guanine nucleotide exchange factor;    Membrane translocation;    G protein;    guanine nucleotide binding protein;    RGS;    regulator of G protein signaling;    Rho;    Ras homology;    GEF;    guanine nucleotide exchange factor;    DH;    Dbl homology;    PH;    pleckstrin homology;    GAP;    GTPase activating protein;    GPCR;    G protein-coupled receptor;   

DOI  :  10.1016/S0014-5793(03)00267-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The Ras homology (Rho) guanine nucleotide exchange factor p115-RhoGEF couples the α₁₃ heterotrimeric guanine nucleotide binding protein (G protein) subunit to Rho GTPase. α₁₃ binds to a regulator of G protein signaling (RGS) domain in p115-RhoGEF, but the mechanism of α₁₃ activation of p115-RhoGEF is poorly understood. In this report, we demonstrate in cell-based assays that the acidic-rich N-terminus, adjacent to the RGS domain, is required for binding to activated α₁₃, and refine the importance of this region by showing that mutation of glutamic acids 27 and 29 in full-length p115-RhoGEF is sufficient to prevent interaction with activated α₁₃. However, α₁₃-interacting deficient N-terminal mutants of p115-RhoGEF retain α₁₃-dependent plasma membrane recruitment. Overall, these findings demonstrate a critical role for the N-terminal extension of p115-RhoGEF in mediating binding to α₁₃ and dissociate two activities of p115-RhoGEF: binding to activated α₁₃ and translocation to the PM in response to activated α₁₃.

【 授权许可】

Unknown