TY - JOUR
T1 - Regulation of angiotensin II-induced G protein signaling by phosducin-like protein
AU - McLaughlin, Joseph N.
AU - Thulin, Craig D.
AU - Bray, Steven M.
AU - Martin, Mickey M.
AU - Elton, Terry S.
AU - Willardson, Barry M.
PY - 2002/9/20
Y1 - 2002/9/20
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M205583200
DO - 10.1074/jbc.M205583200
M3 - Article
C2 - 12107186
AN - SCOPUS:0037144570
SN - 0021-9258
VL - 277
SP - 34885
EP - 34895
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 38
ER -