Plasma membrane signal-transducing ATP

Abstract

Plasma membranes of target cells generate considerable amounts of ATP in response to binding of growth factors, cytokines, and oncoproteins. Plasma membrane ATP is formed at the stage of ligand-receptor signal transduction by the anaerobic pathway with the involvement of plasma membrane redox systems and Na* (but not adenylate cyclase). The assumption on the involvement of transitory reversed Na+,K+-ATPase in the synthesis of plasma membrane ATP is confirmed by inhibitory analysis. ATP-producing activity of plasma membrane-enriched particles isolated from various target cells in response to various growth factors was studied. The formation of plasma membrane ATP is stimulated by growth factors and cytokines interacting with integral tyrosine kinase receptors or soluble tyrosine kinases in the cytosol. Various tyrosine kinase inhibitors act by utilizing plasma membrane ATP. Plasma membrane ATP is assumed to be a messenger and amplifier of ligand-receptor signals in plasma membranes of animal cells. Key Words: plasma membrane; ATP; growth factors; transmembrane signaling; oncogenesisPhosphorylation is the main mechanism responsible for induction or suppression of cell activity and realization of the major biological processes. Disturbances in the regulation of this mechanism cause a number of diseases [6,13,22,38,39].A new class of hormone-like compounds, polypeptide growth factors and cytokines involved in proliferation, differentiation, and transformation of many types of cells, including immunocompetent cells, was discovered over the past decades [19,34] [26,27]. A general concept of the main mechanism of transmission and amplification of extracellular signals for cell growth, proliferation, mitogenesis, differentiation, and chemotaxis perceived by membrane receptors was derived from these data.Tyrosine kinases play the major role in the transduction of receptor-mediated extracellular signals for cell growth, proliferation, differentiation, and oncogenesis [31][32][33]54]. Extracellular signals are transduced by intracellular messengers coupled with the corresponding protein kinases. However, the central mechanism responsible for activation of tyrosine kinases remains unclear. HistoryIn 1980, it was shown that the preparation of plasma membrane-enriched particles (PMEP) from rat skeletal muscles in a medium containing Tris-HCl (pH 7.5),

Effect of Melafen on Structure and Function of Liposome and Ehrlich Ascitic Carcinoma Cell Membranes

“…This was paralleled by stimulation of phospholipase C activity, increase of plasma concentration of inositol triphosphate releasing Ca 2+ from intracellular Ca 2+ depot (endoplasmic reticulum) [12][13][14]. The intracellular concentration of Ca 2+ sharply increases and Ca 2+ -dependent plasmalemma K + and Cl -channels are activated, which leads to modification of cell volume [4]. A signal about exhaustion of Ca 2+ depots is delivered to the cell plasmalemma, the channels of capacitative Ca 2+ entry are activated.…”