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  • The EMBO Journal (2005) 24, 1965 - 1975
  • doi:10.1038/sj.emboj.7600673

Published online: 5 May 2005

Phosducin-like protein acts as a molecular chaperone for G protein bold betabig gamma dimer assembly

Georgi L Lukov1, Ting Hu1, Joseph N McLaughlin2, Heidi E Hamm2 and Barry M Willardson1

  1. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA
  2. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA

Correspondence to:

Barry M Willardson, Department of Chemistry and Biochemistry, Brigham Young University, C210 BNSN, Provo, UT 84602, USA. Tel.: +1 801 422 2785; Fax: +1 801 422 0153; E-mail: barry_willardson@byu.edu

Received 4 March 2005; Accepted 11 April 2005

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.

  • Keywords:

    • chaperonin,
    • CK2 phosphorylation,
    • G protein,
    • phosducin-like protein,
    • protein folding