Experimental approaches to understanding the role of protein phosphorylation in the regulation of neuronal function.

Studies by Earl Suthcrland and his eollcagucs onhormonal regulation f the breakdown ofglycogen i liver esulted inthe discovery that the first step in the action of many hormones is to increase the synthesis ofcAMP by activating adcnylatc eyelase (Raft ct al 1957, Sutherland & Rall 1958, Robison ctal 1968). It was later established that cAMP exerts its elfects by stimulating protein kinascs that catalyze the phosphorylation of specific functional proteins and thereby regulate heir activity (Walsh et al 1968, Kuo & Crrccngard 1969, Krcbs & Bcavo 1979). The discovery that the brain contains a high concentration of cAMP-dependent protein kinase led to the proposal that protein phosphorylation might play an important role in regulation fneuronal properties byncurotransmittcrs and ncurohormones fMiyamoto ctal 1969). In particular, it sccmcd that protein phosphorylation, which usually takes place on a time scale of hundreds ofmilliseconds or longer, might bc a mcchanism underlying relatively long-lasting changes in neuronal properties such as "slow" changes in post-synaptic potentials (McAfec & Greengard 1972), changes in the rate of transmitter synthesis (Morgenroth etal 1975), or changes m gcnc expression (Klein & Berg 1970). The biochemists andncurobiologists who took up the study of brain protein phosphorylation hoped to gain insight into some of the mechanisms