Cell Responses Initiated by Ecto-Kinases
The effects of extracellular adenosine triphosphate (ATP) on cells clearly involve binding interactions with P2 receptors, which initiate transduction and responses mediated by intracellular messengers. It is tacitly assumed that, like non-nucleotide agonists, the binding of ATP and its synthetic congeners at the receptors involves a reversible association-dissociation phenomenon in which this high energy phosphate-containing nucleotide is not changed chemically as a consequence. Much evidence indicates that, in addition to the extracellular receptors for ATP, many types of cells possess on their outer membrane surface one or more kinase enzymes, referred to as “ecto-kinases” (“EK”) because of their location, that utilize the γ-phosphate of ATP to phos-phorylate proteins. The phosphorylated proteins may reside in or on the cell membrane, in which case they are referred to as “endogenous” substrates. EK may also phosphorylate proteins in the extracellular milieu; these substrates are referred to as “exogenous” substrates. The relationship of these phosphorylation events to cell processes is not apparent in most cases. There are a few examples in which the relationship between phosphorylation and function seem well correlated, but usually the biochemical evidence for phosphorylation precedes and is better established than functional significance.
KeywordsDopamine Tyrosine Fluoride Heparin Vanadate
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- Agren, G. and Ronquist, G. (1971) Isolation of 32P-labelled phosphorylserine and phosphoryl-threonine from Ehrlich mouse-ascites tumour cells, suspended in an isotonic medium, containing 32P-labelled nucleoside triphosphates or inorganic pyrophosphates. Acta Chem. Scand. 25, 2931–2934.PubMedCrossRefGoogle Scholar
- Barua, M., Haldar, S., and Majumder, G.C. (1990) Occurrence of a coupled-enzyme system on the intact-sperm outer surface that phosphorylates and dephosphorylates ecto-proteins. Biochem. Intl. 20, 1089–1096.Google Scholar
- Chen, X. Y. and Lo, T. C. Y. (1991b) Phosphorylation of a cell surface 112 kDa protein by an ecto-protein kinase in rat L6 myoblasts. Biochem. J. 279, 464–474.Google Scholar
- Fedan, J. S., Hogaboom, G. K., Westfall, D. P., and O’Donnell, J. P. (1982a) Comparison of the effects of arylazido aminopropionyl ATP (ANAPP3), an ATP antagonist, on responses of the smooth muscle of the guinea-pig vas deferens to ATP and related nucleotides. Eur. J. Pharmacol. 85, 277–290.PubMedCrossRefGoogle Scholar
- Fujii, S., Kato, H., Furuse, H., Ito, K.-I., Osada, H., Hamaguchi, T., and Kuroda, Y. (1995a) The mechanism of ATP-induced long-term potentiation involves extracellular phosphorylation of membrane proteins in guinea-pig hippocampal CA1 neurons. Neurosci. Lett. 187, 130–132.PubMedCrossRefGoogle Scholar
- Haldar, S., Dey, C. S., and Majumder, G. C. (1986) An ecto-cyclic AMP-independent protein kinase in goat spermatozoa and its change of activity during forward motility. Biochem. Int. 13, 609–617.Google Scholar
- Ihara, S., Maeda-Takekoshi, F., Takekoshi, M., Yokoyama, M., Sakuma, S., and Watanabe, Y. (1991) Evidence that the tyrosine kinase domain of a small fraction of epidermal growth factor receptor molecules is exposed on the outer surface of A431 cells. Cell Struct Funct. 16, 217–223.PubMedCrossRefGoogle Scholar
- Kübler, D., Pyerin, W., Bill, O., Hotz, A., Sonka, J., and Kinzel, V. (1989) Evidence for ecto-protein kinase activity that phosphorylates Kemptide in a cyclic AMP-dependent mode. J. Biol. Chem. 264, 14, 549-614, 555.Google Scholar
- Ronquist, G. and Agren, G. (1974) Isolation of 32P-labeled phosphorylserine and phosphorylthreonine from Ehrlich mouse ascites tumor cells suspended in different isotonic media containing 32P-labeled adenosine triphosphate. Acta Chem. Scand. Series B. Org. Chem. Biochem. 28, 1169–1174.CrossRefGoogle Scholar
- Skubitz, K. M., Ducker, T. P., Skubitz, A. P. N., and Goueli, S. A. (1993) Antiserum to carcinoembryonic antigen recognizes a phosphotyrosine-containing protein in human colon cancer cell lines. J. Immunol. 318, 200–204.Google Scholar
- Skubitz, K. M. and Ehresmann, D. D. (1992) The angiogenesis inhibitor β-cyclodextrin tetradecasulfate inhibits ecto-protein kinase activity. Cell. Molec. Biol. 38, 543–560.Google Scholar
- Soltoff, S. P., McMillian, M. K., Lechleiter, J. D., Cantley, L. C., and Talamo, B. R. (1990) Elevation of [Ca2+]i and the activation of ion channels and fluxes by extracellular ATP and phospholipase C-linked agonists in rat parotid acinar cells. Ann. NY Acad. Sci. 603, 76–92.PubMedCrossRefGoogle Scholar