Phosphoproteins, neuronal

Neuronal phosphoproteins differ considerably in the number and types of amino acid residues phosphorylated 402... 

This list is not intended to be comprehensive but to indicate the wide array of neuronal proteins regulated by phosphorylation. Some of the proteins are specific to neurons but most are present in many cell types in addition to neurons and are included because their multiple functions in the nervous system include the regulation of neuron-specific phenomena. Not included are the many phosphoproteins present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that do not appear to play a role in neuron-specific phenomena. NMDA, N-methyl-D-aspartate CREB, cAMP response element-binding proteins STAT, signal-transducing activators of transcription ... 

Neuronal phosphoproteins differ considerably in the number and types of amino acid residues phospho-rylated. The complexity of intracellular regulation is underscored by the now numerous and well-established observations of numerous proteins that are phosphory-lated on more than one amino acid residue by more than... 

To illustrate some of the roles played by protein phosphorylation in the regulation of nervous system function, some well characterized neuronal phosphoproteins and some aspects of neurotransmission regulated by phosphorylation in the pre- and postsynaptic compartments are discussed in detail. 

Increasing evidence indicates that a chronic opiate-induced upregulation of the cAMP pathway, manifested by increased concentrations of adenylyl cyclase, PKA and several phosphoprotein substrates for the protein kinase, contributes to opiate tolerance, dependence and withdrawal exhibited by locus ceruleus neurons [66]. This upregulated cAMP pathway can be viewed as a homeostatic response of the neurons to persistent opiate inhibition of the cells. In the chronic opiate-treated state, the upregulated cAMP pathway helps return neuronal firing rates to control levels, i.e. tolerance. Upon abrupt removal of the opiate via the administration of an opiate receptor antagonist, the upregulated cAMP accounts for part of the withdrawal activation of the cells. 

Uberti, D., Belloni, M., GriUi, M., Spano, P., and Memo, M., 1998. Induction of tumor suppressor phosphoprotein p53 in the apoptosis of cultured rat cerebellar neurones triggered by excitatory amino acids. Eur. J. Neurosci 70 246-254. 

Dolphin AC, Goelz SE, Greengard P (1980) Neuronal protein phosphorylation recent studies concerning protein I, a synapse-specific phosphoprotein. Pharmacol Biochem Behav 13 Suppl 1 169-74 169-74... 

Grebb JA, Greengard P. 1990. An analysis of synapsin II, a neuronal phosphoprotein, in postmortem brain tissue from alcoholic and neuropsychiatrically ill adults and medically ill children and young adults. Arch Gen Psychol 47 1149-1156. 

Hemmings HC, Jr, Nairn AC, Greengard P (1984a) DARPP-32, a dopamine- and adenosine 3 5 -monophosphate-regulated neuronal phosphoprotein. II. Comparison of the kinetics of phosphorylation of DARPP-32 and phosphatase inhibitor 1. J Biol Chem 259 14491-14497. 

Hemmings HC, Jr, Greengard P, Tung HY, Cohen P (1984b) DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature 370 503-505. 

Greengard, P. (1987) Neuronal phosphoproteins. Mediators of signal transduction. Mol. Neurobiol. 1 81-119. 

In the cerebellum type I NOS and components of the cGMP signaling system are localized to a subset of cells (Schmidt et al., 1993). Purkinje cells are enriched in soluble guanylate cyclase and GKI, and neuron-specific GKI substrate protein is phosphorylated in these cells. The phosphoprotein reportedly affects neuronal signaling by inhibition of protein phosphatases 1 and 2A (Schmidt et al., 1993). 

There are two direct consequences of insulin binding to the receptor. First the tyrosine kinase activity on the / -subunit is activated. This causes autophosphorylation and also phosphorylation of intracellular proteins. Although a number of proteins have been phosphorylated in vitro, it is not yet clear what is the normal physiological substrate or substrates. In mammals, several cellular protein substrates have been proposed, but the precise role of any of the proteins is unclear. A 70 kDa protein has been proposed as a substrate in cultured foetal chick neurons, and a 72 kDa phosphoprotein in domestic fowl hepatoma, but the functions of these polypeptides are unclear (Simon Taouis, 1993). Second, binding causes internalisation of the receptor, after which the insulin is removed and degraded in the lysosomes and the receptor recycled back to the plasmalemma. In domestic fowl hepatocytes, the half-life of the receptor is about 10 h (Simon, 1989). 

RamaRao, G., Bhattacharya, B.K., Kumar, S., et al., 2011. Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication. Toxicol 293, 195-202. 

Byrne JH, Zwatijes R, Homayouni R, Critz SD, Eskin A. Roles of second messenger pathways in neuronal plasticity and in learning and memory. Insights gained from Aplysia. In Shenolikar S, Nairn AC, eds. Advances Second Messengers Phosphoprotein. Res Vol. 27, New York Raven Press, 1993 47-108. 

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