The pathway connecting m2 receptors to the nucleus involves small GTP-binding proteins acting on divergent MAP kinase cascades.
m1 and m2 receptors are traditionally linked to tissue specific functions performed by fully differentiated cells. However, these receptors have been also implicated in growth stimulation. The mechanisms whereby these receptors regulate proliferative signaling pathways are still poorly understood. Furthermore, pharmacological evidence suggest that many growth promoting agents act on Gi coupled receptors, but there is no formal proof that induction of DNA-synthesis results from decreased intracellular levels of cAMP. In our laboratory, we have used the expression of ml and m2 receptors as a model for studying proliferative signaling through G protein-coupled receptors. Currently available evidence suggest that these receptors signal to distinct members of the MAP kinase superfamily, MAP kinase and JNK, through betagamma subunits of heterotrimeric G proteins acting, respectively, on a Ras and Rac1 dependent pathway.
Gutkind
J S
JS
Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
Crespo
P
P
Xu
N
N
Teramoto
H
H
Coso
O A
OA
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction
D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins