Ecto-protein kinase activity on the external surface of neural cells

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Abstract
ATP is secreted in association with neurotransmitters at certain synapses and neuromuscular junctions1,2. Extracellular ATP is known to exert potent effects on the activity of cells in the nervous system, where it can act as a neurotransmitter or as a modulator regulating the activity of other neurohormones3–5. We have suggested that such modulation may involve the activity of extracellular protein phosphorylation systems6. It is well known that intracellular protein kinases are important in the regulation of various neuronal functions6–8, but protein kinases which use extracellular ATP to phosphorylate proteins localized at the external surface of the plasma membrane (ecto-protein kinases) have not been demonstrated in neuronal cells. Here we present direct evidence for the existence of an ecto-protein kinase and demonstrate endogenous substrates for its activity at the surface of intact neural cells. The phosphorylation of one of these surface proteins is selectively stimulated during cell depolarization. In addition, neuronal cell adhesion molecules (N-CAMs) appear to be among the substrates of ecto-protein kinase activity. These results suggest a role for surface protein phosphorylation in regulating specific functions of developing and mature neurones.