TYR-MIF-1, but not MIF-1 or morphine, decreases cyclic AMP-dependent protein kinase activity extracted from HeLa cells.
The biochemical effects of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH(2)), a naturally occurring opiate modulator, on cellular function are poorly understood. We looked for changes in cyclic AMP-dependent protein kinase (cAMP-kinase; protein kinase A) after treating HeLa cells with this peptide. Binding sites for Tyr-MIF-1 (IC(50) = 83 nM), but not for DAMGO, a mu opiate, were found on these cells. Brief incubation of HeLa cells with 10(-7) to 10(-5)M Tyr-MIF-1 significantly decreased, in a rapid and dose-dependent manner, cAMP-kinase activity in cell extracts assayed in reaction mixtures with added cAMP but not the much lower basal enzymatic activity that is dependent on endogenous cAMP. In contrast, incubation of the cells with the related peptide MIF-1 (Pro-Leu-Gly-NH(2)) or with morphine did not significantly alter cAMP-kinase activity. This study shows that Tyr-MIF-1 can affect part of a major signal transduction pathway independently of binding to opiate receptors.
Zhang
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Department of Biochemistry, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Zadinat
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Ehrlich
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Kastint
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AJ