Wan Y, Kurosaki T, Huang X Y
Department of Physiology, Cornell University Medical College, New York 10021, USA.
Nature. 1996 Apr 11;380(6574):541-4. doi: 10.1038/380541a0.
The mitogen-activated protein kinase (MAPK) signalling cascade is a prominent cellular pathway used by many growth factors, hormones and neurotransmitters to regulate physiological responses. Although activation of the MAPK pathway by receptors with tyrosine kinase activity is well defined, the mechanism used by heterotrimeric G-protein-coupled receptors to activate this pathway is less clear. Here we show that in cells deficient in the Src-related tyrosine kinase Lyn, stimulation of MAPK kinase and MARPK by Gq-coupled m1 muscarinic acetylcholine receptors (mAChR) is blocked, whereas Gi-coupled m2 mAChR-mediated stimulation is unaffected. In cells deficient in the tyrosine kinase Syk, both m1 and m2 mAChRs failed to stimulate MAPK kinase and MAPK. This result indicates that Syk is essential for the Gi-coupled pathway and that Lyn and Syk are necessary for the Gq-coupled pathway.
丝裂原活化蛋白激酶（MAPK）信号级联是许多生长因子、激素和神经递质用来调节生理反应的重要细胞途径。虽然具有酪氨酸激酶活性的受体对MAPK途径的激活已得到充分阐明，但异源三聚体G蛋白偶联受体激活该途径的机制尚不清楚。在这里，我们表明，在缺乏Src相关酪氨酸激酶Lyn的细胞中，由Gq偶联的m1毒蕈碱型乙酰胆碱受体（mAChR）对MAPK激酶和MAPK的刺激被阻断，而Gi偶联的m2 mAChR介导的刺激不受影响。在缺乏酪氨酸激酶Syk的细胞中，m1和m2 mAChR均未能刺激MAPK激酶和MAPK。这一结果表明，Syk对于Gi偶联途径至关重要，而Lyn和Syk对于Gq偶联途径是必需的。
