Regulation of angiotensin II-induced G protein signaling by phosducin-like protein

Joseph N. McLaughlin, Craig D. Thulin, Steven M. Bray, Mickey M. Martin, Terry S. Elton, Barry M. Willardson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Phosducin-like protein (PhLP) is a broadly expressed member of the phosducin (Pd) family of G protein βγ subunit (Gβγ)-binding proteins. Though PhLP has been shown to bind Gβγ in vitro, little is known about its physiological function. In the present study, the effect of PhLP on angiotensin II (Ang II) signaling was measured in Chinese hamster ovary cells expressing the type 1 Ang II receptor and various amounts of PhLP. Up to 3.6-fold overexpression of PhLP had no effect on Ang II-stimulated inositol trisphosphate (IP3) formation, whereas further increases caused an abrupt decrease in IP3 production with half-maximal inhibition occurring at 6-fold PhLP overexpression. This threshold level for inhibition corresponds to the cellular concentration of cytosolic chaperonin complex, a recently described binding partner that preferentially binds PhLP over Gβγ. Results of pertussis toxin sensitivity, GTPγS binding, and immunoprecipitation experiments suggest that PhLP inhibits phospholipase Cβ activation by dual mechanisms: (i) steric blockage of Gβγ activation of PLCβ and (ii) interference with Gβγ-dependent cycling of Gqα by the receptor. These results suggest that G protein signaling may be regulated through controlling the cellular concentration of free PhLP by inducing its expression or by regulating its binding to the chaperonin.

Original languageEnglish (US)
Pages (from-to)34885-34895
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number38
DOIs
StatePublished - Sep 20 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    McLaughlin, J. N., Thulin, C. D., Bray, S. M., Martin, M. M., Elton, T. S., & Willardson, B. M. (2002). Regulation of angiotensin II-induced G protein signaling by phosducin-like protein. Journal of Biological Chemistry, 277(38), 34885-34895. https://doi.org/10.1074/jbc.M205583200