Albumin: a Galpha(s)-specific guanine nucleotide dissociation inhibitor and GTPase activating protein.
Heterotrimeric GTP binding protein (G protein)-mediated signal transduction events are regulated by their effectors and regulators of G protein signaling (RGS) protein family. The latter proteins function as GTPase activating proteins (GAPs) for G protein alpha subunits and terminate signaling events. In a search for proteins that modulate the activity of the stimulatory G protein of adenylyl cyclase (Galpha(s)), we found that bovine serum albumin (BSA) inhibits the steady-state GTPase activity of Galpha(s), but not the inhibitory G protein (Galpha(i1)). This effect of BSA is mediated by decreasing the rate of GDP dissociation from Galpha(s) and decreasing the rate of GTP binding. Thus, BSA functions as a guanine nucleotide dissociation inhibitor for Galpha(s). Moreover, BSA also increased the intrinsic GTPase activity of Galpha(s), but not Galpha(i1), demonstrating that BSA functions as a Galpha(s)-specific GAP. Using mutants of Galpha(s) (Q227L, Q227N, R201C, and R201K), we demonstrate that BSA mediates its GAP function by modulating the ability of R201 to increase GTPase activity. Moreover, using wild-type and Q227N forms of Galpha(s), our studies demonstrate that the GDI function of BSA decreases the ability of Galpha(s) to stimulate adenylyl cyclase. These findings assign a novel function to BSA as a regulator of G protein signaling.
Du
Ziyun
Z
Department of Pharmacology, University of Tennessee, The Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA.
Patel
Tarun B
TB
D000262:Adenylyl Cyclases / Q000737:chemistry; D000418:Albumins / Q000737:chemistry; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D020558:GTP Phosphohydrolases / Q000737:chemistry*; D019204:GTP-Binding Proteins / Q000737:chemistry*; D020690:GTPase-Activating Proteins / Q000737:chemistry*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry*; D021122:Protein Subunits / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry*
D000418:Albumins; D004791:Enzyme Inhibitors; D020690:GTPase-Activating Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D021122:Protein Subunits; D012710:Serum Albumin, Bovine; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases