Alterations in the subcellular distribution of p21ras-GTPase activating protein in proliferating rat acinar cells

Rat parotid acinar cells undergo transient proliferation in response to chronic administration of the beta-adrenergic agonist isoproterenol or epidermal growth factor (EGF). Treatment with these agents caused an increase in tyrosine phosphorylation of p21ras-GTPase activating protein (GAP). This phosphorylation event was accompanied by a redistribution of the protein from the plasma membrane to internal membrane compartments. Separation of subcellular membranes revealed increased GAP associated with a low density population of vesicles concomitant with growth stimulation as well as to the nuclear membrane, but not the nucleoplasm. Upon cessation of hyperplasia induced by isoproterenol, phosphorylated GAP present in the plasma membrane returned to control cell levels.