TY - JOUR
T1 - Gγ-like (GGL) domains
T2 - New frontiers in G-protein signaling and β-propeller scaffolding
AU - Sondek, John
AU - Siderovski, David P.
N1 - Funding Information:
Our thanks to Ryan Watkins for assistance in modelling the RACK1/PDE4D5 interaction and T. Kendall Harden for critical review of this commentary and unwavering support. The authors are supported by NIH Grants GM57391 (J.S.), and GM62338 (D.P.S.). J.S. is a Scholar of the Pew Charitable Trusts, and D.P.S. is a Scholar of the EJLB Foundation. J.S. is a Scholar of the Pew Charitable Trusts and D.P.S. is a scholar of the EJLB Foundation and a recipient of a New Investigator Award in The Basic Pharmacological Sciences from the Burroughs Wellcome fund.
PY - 2001/6/1
Y1 - 2001/6/1
N2 - The standard model of signal transduction from G-protein-coupled receptors (GPCRs) involves guanine nucleotide cycling by a heterotrimeric G-protein assembly composed of Gα, Gβ, and Gγ subunits. The WD-repeat β-propeller protein Gβ and the alpha-helical, isoprenylated polypeptide Gγ are considered obligate dimerization partners; moreover, conventional Gβγ heterodimers are considered essential to the functional coupling of Gα subunits to receptors. However, our recent discovery of a Gβ5 binding site (the Gγ-like or "GGL" domain) within several regulators of G-protein signaling (RGS) proteins revealed the potential for functional GPCR/Gα coupling in the absence of a conventional Gγ subunit. In addition, we posit that the interaction between Gβ5 isoforms and the GGL domains of RGS proteins represents a general mode of binding between β-propeller proteins and their partners, extending beyond the realm of G-protein-linked signal transduction.
AB - The standard model of signal transduction from G-protein-coupled receptors (GPCRs) involves guanine nucleotide cycling by a heterotrimeric G-protein assembly composed of Gα, Gβ, and Gγ subunits. The WD-repeat β-propeller protein Gβ and the alpha-helical, isoprenylated polypeptide Gγ are considered obligate dimerization partners; moreover, conventional Gβγ heterodimers are considered essential to the functional coupling of Gα subunits to receptors. However, our recent discovery of a Gβ5 binding site (the Gγ-like or "GGL" domain) within several regulators of G-protein signaling (RGS) proteins revealed the potential for functional GPCR/Gα coupling in the absence of a conventional Gγ subunit. In addition, we posit that the interaction between Gβ5 isoforms and the GGL domains of RGS proteins represents a general mode of binding between β-propeller proteins and their partners, extending beyond the realm of G-protein-linked signal transduction.
KW - G-gamma-like (GGL) domain
KW - Guanine nucleotide-binding protein (G protein)
KW - Kinesin
KW - PDE4D5
KW - RACK1
KW - Regulators of G-protein signaling (RGS) proteins
UR - http://www.scopus.com/inward/record.url?scp=0035354341&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(01)00633-5
DO - 10.1016/S0006-2952(01)00633-5
M3 - Article
C2 - 11331068
AN - SCOPUS:0035354341
SN - 0006-2952
VL - 61
SP - 1329
EP - 1337
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -