Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly.
Phosducin-like protein (PhLP) is a widely expressed binding partner of the G protein betagamma subunit dimer (Gbetagamma). However, its physiological role is poorly understood. To investigate PhLP function, its cellular expression was blocked using RNA interference, resulting in inhibition of Gbetagamma expression and G protein signaling. This inhibition was caused by an inability of nascent Gbetagamma to form dimers. Phosphorylation of PhLP at serines 18-20 by protein kinase CK2 was required for Gbetagamma formation, while a high-affinity interaction of PhLP with the cytosolic chaperonin complex appeared unnecessary. PhLP bound nascent Gbeta in the absence of Ggamma, and S18-20 phosphorylation was required for Ggamma to associate with the PhLP-Gbeta complex. Once Ggamma bound, PhLP was released. These results suggest a mechanism for Gbetagamma assembly in which PhLP stabilizes the nascent Gbeta polypeptide until Ggamma can associate, resulting in membrane binding of Gbetagamma and release of PhLP to catalyze another round of assembly.
Lukov
Georgi L
GL
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Hu
Ting
T
McLaughlin
Joseph N
JN
Hamm
Heidi E
HE
Willardson
Barry M
BM
D002352:Carrier Proteins; D047390:Casein Kinase II / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology
D002352:Carrier Proteins; C410342:GNG2 protein, human; D044387:GTP-Binding Protein beta Subunits; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C098789:PDCL protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D047390:Casein Kinase II; D019204:GTP-Binding Proteins