Insulin-like effect of zinc in Mytilus digestive gland cells: Modulation of tyrosine kinase-mediated cell signaling

The possible effects of zinc in the modulation of the activity of glycolyti c enzymes phosphofructokinase and pyruvate kinase through tyrosine kinase-m ediated signal transduction in isolated digestive gland cells from mussels (Mytilus galloprovincialis Lam.) were investigated. Addition of micromolar concentrations of zinc resulted in both time- and concentration-dependent s timulation of glycolytic enzyme activities similar to those previously obse rved with insulin; however, zinc pretreatment prevented the glycolytic effe ct of insulin in mussel cells. The insulin-like effect of zinc was mediated by increased tyrosine phosphorylation of multiple proteins, as demonstrate d by Western blotting with antiphosphotyrosine antibodies. The pattern of z inc-induced phosphorylation resembled that induced by insulin. Moreover, bo th zinc and insulin induced activation of mitogen activated protein kinases (MAPKs);however, whereas zinc gave a clear effect on the stress-activated p-38 MAPK, insulin activated extracellular-activated MAPK (ERK2) and inhibi ted p-38. The results demonstrate that zinc can act as a physiological regu lator of tyrosine kinase-mediated cell signaling in mussel digestive gland cells, in particular at the level of MAPK activation. Activation of p-38 by zinc may be a key step in prevention of the glycolytic effect of insulin i n mussel cells. These data underline the importance of cross talk between d ifferent MAPKs in determination of the response to extracellular stimuli in marine invertebrate cells. (C) 2001 Academic Press.