通过核苷酸交换和GTP水解对M1毒蕈碱受体-Gq-磷脂酶C-β途径的调节。

Regulation of the M1 muscarinic receptor-Gq-phospholipase C-beta pathway by nucleotide exchange and GTP hydrolysis.

作者信息

Ross E M, Berstein G

机构信息

Department of Pharmacology, University of Texas, Southwestern Graduate School of Biomedical Sciences, Dallas 75235-9041.

出版信息

Life Sci. 1993;52(5-6):413-9. doi: 10.1016/0024-3205(93)90296-f.

DOI:10.1016/0024-3205(93)90296-f

PMID:8441322

Abstract

M1 muscarinic cholinergic receptors, G1 and G11 (Gq/11), and phospholipase C-beta 1 were highly purified from both natural sources and cells that express the appropriate cDNA's. When the proteins were co-reconstituted into phospholipid vesicles, the receptor efficiently and selectively promoted the activation of Gq/11, leading to marked stimulation of PLC activity in the presence of GTP gamma S. No stimulation was observed in the presence of GTP, however, which led to the finding that PLC-beta 1 stimulates the hydrolysis of GQ/11-bound GTP at least 50-fold. Thus, PLC-beta 1 is a GTPase activating protein, a GAP, for its physiologic regulator Gq/11. We discuss the implications of PLC-beta 1's GAP activity on the M1 muscarinic cholinergic signaling pathway.

摘要

M1毒蕈碱型胆碱能受体、G1和G11（Gq/11）以及磷脂酶C-β1均从天然来源和表达相应cDNA的细胞中高度纯化。当这些蛋白质共重组到磷脂囊泡中时，该受体高效且选择性地促进Gq/11的激活，在存在GTPγS的情况下导致磷脂酶C活性受到显著刺激。然而，在存在GTP的情况下未观察到刺激作用，这导致发现磷脂酶C-β1刺激与Gq/11结合的GTP水解至少50倍。因此，磷脂酶C-β1是其生理调节因子Gq/11的一种GTP酶激活蛋白（GAP）。我们讨论了磷脂酶C-β1的GAP活性对M1毒蕈碱型胆碱能信号通路的影响。