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

Georgi L. Lukov, Ting Hu, Joseph N. McLaughlin, Heidi E. Hamm, Barry M. Willardson

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)1965-1975
Number of pages11
JournalEMBO Journal
Volume24
Issue number11
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

Molecular Chaperones
GTP-Binding Proteins
Dimers
Proteins
Phosphorylation
Chaperonin Containing TCP-1
Chaperonins
phosducin
Casein Kinase II
Protein Subunits
RNA Interference
Serine
RNA
Membranes
Peptides

Keywords

  • Chaperonin
  • CK2 phosphorylation
  • G protein
  • Phosducin-like protein
  • Protein folding

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Phosducin-like protein acts as a molecular chaperone for G protein βγ dimer assembly. / Lukov, Georgi L.; Hu, Ting; McLaughlin, Joseph N.; Hamm, Heidi E.; Willardson, Barry M.

In: EMBO Journal, Vol. 24, No. 11, 01.06.2005, p. 1965-1975.

Research output: Contribution to journalArticle

Lukov, Georgi L. ; Hu, Ting ; McLaughlin, Joseph N. ; Hamm, Heidi E. ; Willardson, Barry M. / Phosducin-like protein acts as a molecular chaperone for G protein βγ dimer assembly. In: EMBO Journal. 2005 ; Vol. 24, No. 11. pp. 1965-1975.
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