Winitz S, Russell M, Qian N X, Gardner A, Dwyer L, Johnson G L
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
J Biol Chem. 1993 Sep 15;268(26):19196-9.
Stimulation of the acetylcholine muscarinic m2 receptor (m2R) expressed in Rat 1a fibroblasts results in the activation of the cytoplasmic mitogen-activated protein kinase (MAPK). Concomitant with carbachol stimulation of the m2R was the activation of MEK (MAPK kinase) and Raf. MEK is the dual function kinase that phosphorylates and activates MAPK. Raf is a serine/threonine kinase capable of phosphorylating and activating MEK. Carbachol stimulation of the m2R also activated Ras. Pertussis toxin treatment of Rat 1a cells inhibited the m2R-mediated activation of Ras, Raf, MEK and MAPK. In contrast, epidermal growth factor receptor-mediated activation of Ras, Raf, MEK and MAPK was pertussis toxin-insensitive. m2R activation of Ras, Raf, and MAPK was insensitive to inhibition by genistein, while the epidermal growth factor receptor-induced responses were inhibited by genistein. The findings demonstrate that both Ras and Raf can be regulated by seven-membrane-spanning receptors that selectively couple to Gi proteins.
在大鼠1a成纤维细胞中表达的乙酰胆碱毒蕈碱型m2受体（m2R）受到刺激后，会导致细胞质丝裂原活化蛋白激酶（MAPK）的激活。与卡巴胆碱对m2R的刺激同时发生的是MEK（MAPK激酶）和Raf的激活。MEK是一种双功能激酶，可磷酸化并激活MAPK。Raf是一种丝氨酸/苏氨酸激酶，能够磷酸化并激活MEK。卡巴胆碱对m2R的刺激也激活了Ras。用百日咳毒素处理大鼠1a细胞可抑制m2R介导的Ras、Raf、MEK和MAPK的激活。相反，表皮生长因子受体介导的Ras、Raf、MEK和MAPK的激活对百日咳毒素不敏感。m2R对Ras、Raf和MAPK的激活对金雀异黄素的抑制不敏感，而表皮生长因子受体诱导的反应则受到金雀异黄素的抑制。这些发现表明，Ras和Raf均可由选择性偶联至Gi蛋白的七跨膜受体调节。
