Molecular Cloning of the Growth-factor-activatable Human Na⁺/H⁺ Antiporter

Excerpt

The concentration of cytoplasmic H⁺, like other cations (Ca⁺⁺, Na⁺, ⁺, etc.), is finely regulated in eukaryotic and prokaryotic cells by various types of membrane transporters, channels, or pumps. The concentration of these ions must be tuned within the limit of a narrow window to permit external signals to propagate within the cell and to permit essential metabolic and physiological processes to operate. Intracellular pH (pH_i) is regulated in vertebrate cells by at least three membrane components, which include an amiloride-sensitive Na⁺/H⁺ antiporter, Na⁺-dependent and -independent Cl⁻/HCO⁻₃ antiporters, and presumably some slow active H⁺-extruding system not yet identified (for comprehensive reviews, see Aronson and Boron 1986; Grinstein 1988; Haussinger 1988).

In the context of growth control, pH_i regulation has received much attention because, similar to its occurrence during fertilization of sea urchin eggs, cytoplasmic pH rises rapidly by 0.1–0.3 units in all quiescent cells in response to all mitogens analyzed...