Distinct sequence elements control the specificity of G protein activation by muscarinic acetylcholine receptor subtypes - PubMed (original) (raw)

Distinct sequence elements control the specificity of G protein activation by muscarinic acetylcholine receptor subtypes

J Lechleiter et al. EMBO J. 1990 Dec.

Abstract

Relatively little is understood concerning the mechanisms by which subtypes of receptors, G proteins and effector enzymes interact to transduce specific signals. Through expression of normal, hybrid and deletion mutant receptors in Xenopus oocytes, we determined the G protein coupling characteristics of the functionally distinct m2 and m3 muscarinic acetylcholine receptor (mAChR) subtypes and identified the critical receptor sequences responsible for G protein specificity. Activation of a pertussis toxin insensitive G protein pathway, leading to a rapid and transient release of intracellular Ca2+ characteristic of the m3 receptor, could be specified by the transfer of as few as nine amino acids from the m3 to the m2 receptor. In a reciprocal manner, transfer of no more than 21 residues from the m2 to the m3 receptor was sufficient to specify activation of a pertussis toxin sensitive G protein coupled to a slow and oscillatory Ca2+ release pathway typical of the m2 subtype. Notably, these critical residues occur within the same region of the third cytoplasmic domain of functionally distinct mAChR subtypes.

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References

    1. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767-71 - PubMed
    1. Proc Natl Acad Sci U S A. 1990 Apr;87(8):2896-900 - PubMed
    1. Biochemistry. 1987 May 19;26(10):2657-64 - PubMed
    1. Annu Rev Biochem. 1987;56:615-49 - PubMed
    1. Nature. 1987 Dec 17-23;330(6149):670-2 - PubMed

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