MOLECULAR MECHANISMS OF ANTIPROLIFERATIVE EFFECT OF SOMATOSTATIN - INVOLVEMENT OF A TYROSINE PHOSPHATASE

A protein of 66 kd immunoreactive to anti-tyrosine phosphatase (PTP1C) antibodies coeluted with, and so may be associated with, somatostatin receptors (ssts) from rat pancreatic membranes. Also, anti-PTP1C anti bodies immunoprecipitated functional ssts from pancreatic membranes, s uggesting a PTP1C protein can associate with ssts at the membrane leve l, Somatostatin analog RC 160 had good affinity for sst(2,3) and sst(5 ) (IC50 = 0.2, 0.1, and 21 nmol/L) and low affinity for sst(1) and sst (4) (IC50 = 200 and 620 nmol/L), and induced rapid dose dependent stim ulation of PTP activity (maximal at 1 nmol/L and half maximal at 5 pmo l/L) in NIH373 and CHO cells expressing sst(2), with similar results f or sst(1), but no stimulation with sst(3,4) or sst(5). Treatment of ce lls expressing sst(2) with RC 160 for 24 hours inhibited serum- or gro wth factor-induced cell proliferation dose-dependently (maximal at 1 n mol/L, half maximal at 6 to 53 pmol/L RC 160). In cells expressing sst (1), weak inhibition of fibroblast growth factor 2-induced NIH3T3 cell proliferation was provoked by somatostatin analogs (>10 nmol/L). The good correlation between inhibition of somatostatin binding, stimulati on of PTP activity, and inhibition of cell proliferation implicates a PTP in growth inhibition mediated by sst(2) and sst(1). Copyright (C) 1996 by W.B. Saunders Company