TY - JOUR
T1 - Role of protein phosphorylation in neuronal signal transduction.
AU - Hemmings, H. C.
AU - Nairn, A. C.
AU - McGuinness, T. L.
AU - Huganir, R. L.
AU - Greengard, P.
PY - 1989/3
Y1 - 1989/3
N2 - Protein phosphorylation is involved in the regulation of a wide variety of physiological processes in the nervous system. Studies in which purified protein kinases or kinase inhibitors have been microinjected into defined cells while a specific response is monitored have demonstrated that protein phosphorylation is both necessary and sufficient to mediate responses of excitable cells to extracellular signals. The precise molecular mechanisms involved in neuronal signal transduction processes can be further elucidated by identification and characterization of the substrate proteins for the various protein kinases. The roles of three such substrate proteins in signal transduction are described in this article: 1) synapsin I, whose phosphorylation increases neurotransmitter release and thereby modulates synaptic transmission presynaptically; 2) the nicotinic acetylcholine receptor, whose phosphorylation increases its rate of desensitization and thereby modulates synaptic transmission postsynaptically; and 3) DARPP-32, whose phosphorylation converts it to a protein phosphatase inhibitor and which thereby may mediate interactions between dopamine and other neurotransmitter systems. The characterization of the large number of additional phosphoproteins that have been found in the nervous system should elucidate many additional molecular mechanisms involved in signal transduction in neurons.
AB - Protein phosphorylation is involved in the regulation of a wide variety of physiological processes in the nervous system. Studies in which purified protein kinases or kinase inhibitors have been microinjected into defined cells while a specific response is monitored have demonstrated that protein phosphorylation is both necessary and sufficient to mediate responses of excitable cells to extracellular signals. The precise molecular mechanisms involved in neuronal signal transduction processes can be further elucidated by identification and characterization of the substrate proteins for the various protein kinases. The roles of three such substrate proteins in signal transduction are described in this article: 1) synapsin I, whose phosphorylation increases neurotransmitter release and thereby modulates synaptic transmission presynaptically; 2) the nicotinic acetylcholine receptor, whose phosphorylation increases its rate of desensitization and thereby modulates synaptic transmission postsynaptically; and 3) DARPP-32, whose phosphorylation converts it to a protein phosphatase inhibitor and which thereby may mediate interactions between dopamine and other neurotransmitter systems. The characterization of the large number of additional phosphoproteins that have been found in the nervous system should elucidate many additional molecular mechanisms involved in signal transduction in neurons.
UR - http://www.scopus.com/inward/record.url?scp=0024635938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024635938&partnerID=8YFLogxK
U2 - 10.1096/fasebj.3.5.2493406
DO - 10.1096/fasebj.3.5.2493406
M3 - Review article
C2 - 2493406
AN - SCOPUS:0024635938
SN - 0892-6638
VL - 3
SP - 1583
EP - 1592
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
IS - 5
ER -