Open AccessSelective interaction of the C2 domains of phospholipase C-β 1 and -β 2 with activated Gα q subunits: An alternative function for C2-signaling modules
Author(s) -
Tieli Wang,
Srinivas Pentyala,
John T. Elliott,
Louisa Dowal,
Ekta Gupta,
Mario J. Rebecchi,
Suzanne Scarlata
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.14.7843
Subject(s) - heterotrimeric g protein , gtp' , phospholipase c , g protein , guanosine , gq alpha subunit , protein subunit , biology , isozyme , c2 domain , biochemistry , signal transduction , microbiology and biotechnology , membrane , enzyme , gene
Phospholipase C (PLC)-β1 and PLC-β2 are regulated by the Gq family of heterotrimeric G proteins and contain C2 domains. These domains are Ca2+ -binding modules that serve as membrane-attachment motifs in a number of signal transduction proteins. To determine the role that C2 domains play in PLC-β1 and PLC-β2 function, we measured the binding of the isolated C2 domains to membrane bilayers. We found, unexpectedly, that these modules do not bind to membranes but they associate strongly and specifically to activated [guanosine 5′-[γ-thio]triphosphate (GTP[γS])-bound] Gαq subunits. The C2 domain of PLC-β1 effectively suppressed the activation of the intact isozyme by Gαq (GTP[γS]), indicating that the C2-Gαq interaction may be physiologically relevant. C2 affinity for Gαq (GTP[γS]) was reduced when Gαq was deactivated to the GDP-bound state. Binding to activated Gαi1 subunits or to Gβγ subunits was not detected. Also, Gαq (GTP[γS]) failed to associate with the C2 domain of PLC-δ, an isozyme that is not activated by Gαq . These results indicate that the C2 domains of PLC-β1 and PLC-β2 provide a surface to which Gαq subunits can dock, leading to activation of the native protein.