Tyrosine kinases in activation of the MAP kinase cascade by G-protein-coupled receptors.
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.
Wan
Y
Y
Department of Physiology, Cornell University Medical College, New York 10021, USA.
Kurosaki
T
T
Huang
X Y
XY
D000818:Animals; D001717:Birds; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D000072377:Syk Kinase; D014162:Transfection; D018909:src Homology Domains; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011976:Receptors, Muscarinic; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins