Phosducin-like protein acts as a molecular chaperone for G protein βγ dimer assembly

Phosducin-like protein ( PhLP) is a widely expressed binding partner of the G protein beta gamma subunit dimer (G beta gamma). However, its physiological role is poorly understood. To investigate PhLP function, its cellular expression was blocked using RNA interference, resulting in inhibition of G beta gamma expression and G protein signaling. This inhibition was caused by an inability of nascent G beta gamma to form dimers. Phosphorylation of PhLP at serines 18 - 20 by protein kinase CK2 was required for G beta gamma formation, while a high-affinity interaction of PhLP with the cytosolic chaperonin complex appeared unnecessary. PhLP bound nascent G beta in the absence of G gamma, and S18 - 20 phosphorylation was required for G gamma to associate with the PhLP-G beta complex. Once G gamma bound, PhLP was released. These results suggest a mechanism for G beta gamma assembly in which PhLP stabilizes the nascent Gb polypeptide until G gamma can associate, resulting in membrane binding of G beta gamma and release of PhLP to catalyze another round of assembly.