Phospholipase Cdelta1 is a guanine nucleotide exchanging factor for transglutaminase II (Galpha h) and promotes alpha 1B-adrenoreceptor-mediated GTP binding and intracellular calcium release.
Effectors involved in G protein-coupled receptor signaling modulate activity of GTPases through GTPase-activating protein or guanine nucleotide exchanging factor (GEF). Phospholipase Cdelta1 (PLCdelta1) is an effector in tissue transglutaminase (TGII)-mediated alpha1B-adrenoreceptor (alpha(1B)AR) signaling. We investigated whether PLCdelta1 modulates TGII activity. PLCdelta1 stimulated GDP release from TGII in a concentration-dependent manner, resulting in an increase in GTPgammaS binding to TGII. PLCdelta1 also inhibited GTP hydrolysis by TGII that was independent from the alpha(1B)AR. These results indicate that PLCdelta1 is GEF for TGII and stabilizes the GTP.TGII complex. When GEF function of PLCdelta1 was compared with that of the alpha(1B)AR, the alpha(1B)AR-mediated GTPgammaS binding to TGII was greater than PLCdelta1-mediated binding and was accelerated in the presence of PLCdelta1. Thus, the alpha(1B)AR is the prime GEF for TGII, and GEF activity of PLCdelta1 promotes coupling efficacy of this signaling system. Overexpression of TGII and its mutants with and without PLCdelta1 resulted in an increase in alpha(1B)AR-stimulated Ca2+ release from intracellular stores in a TGII-specific manner. We conclude that PLCdelta1 assists the alpha(1B)AR function through its GEF action and is primarily activated by the coupling of TGII to the cognate receptors.
Baek
K J
KJ
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Kang
S
S
Damron
D
D
Im
M
M
D020013:Calcium Signaling; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D054803:Phospholipase C delta; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D010738:Type C Phospholipases; D054803:Phospholipase C delta; D019204:GTP-Binding Proteins