ISSN:
0730-2312
Keywords:
Gi
;
Gs
;
chimeras
;
adenylyl cyclase
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Gs and Gi, respectively, activate and inhibit the enzyme adenylyl cyclase. Regulation of adenylyl cyclase by the heterotrimeric Gs and Gi proteins requires the dissociation of GDP and binding of GTP to the αs or αi subunit. The βγ subunit complex of Gs and Gi functions, in part, to inhibit GDP dissociation and α subunit activation by GTP. Multiple β and γ polypeptides are expressed in different cell types, but the functional significance for this heterogeneity is unclear. The βγ complex from retinal rod outer segments (βγt) has been shown to discriminate between αi and αs subunits (Helman et al: Eur J Biochem 169:431-439, 1987). βγt efficiently interacts with αi-like G protein subunits, but poorly recognizes the αs subunit. βγt was, therefore, used to define regions of the αi subunit polypeptide that conferred selective regulation compared to the αs polypeptide. A series of α subunit chimeras having NH2-terminal αi and COOH-terminal αs sequences were characterized for their regulation by βγt, measured by the kinetics of GTPγS activation of adenylyl cyclase. A 122 amino acid NH2-terminal region of the αi polypeptide encoded within an αi/αs chimera was sufficient for βγt to discriminate the chimera from αs. A shorter 54 amino acid αi sequence substituted for the corresponding NH2-terminal region of αs was insufficient to support the αi-like interaction with βγt. The findings are consistent with our previous observation (Osawa et al: Cell 63:697-706, 1990) that a region in the NH2-terminal moiety functions as an attenuator domain controlling GDP dissociation and GTP activation of the α subunit polypeptide and that the attenuator domain is involved in functional recognition and regulation by βγ complexes.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240470409
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