Role of protein-tyrosine phosphatases on β-adrenergic receptor mediated morphological differentiation of astrocytes

A role of protein-tyrosine phosphatases in isoproterenol induced differentiation of cultured astrocytes was investigated. Unlike serine/threonine phosphatase inhibitors, the tyrosine phosphatase inhibitor, sodium orthovanadate effectively blocked transformation of the polygonal astrocytes to process bearing stellate cells on exposure to isoproterenol for 2 days. Isoproterenol caused a stimulation of c-AMP dependent protein kinase activity in the cells only at the initial stages (45 min) and at 12 and 24 h, there was a decline in the level of phospho-tyrosinated proteins which could be antagonised by the protein kinase A inhibitor, H89. Genestein, a protein-tyro sine kinase inhibitor, had no effect on the alteration in the morphology of the astroglial cells induced by isoproterenol but by itself, decreased the dephosphorylation of the phospho-tyrosinated proteins, the decline being less than that observed in isoproterenol treated cells. Moreover, unlike H89, genestein had no effect on isoproterenol-induced dephosphorylation of phospho-tyrosinated proteins. Taken together it appears that the dephosphorylation of tyrosine residues during isoproterenol-induced astrocyte differentiation is a downstream event of protein kinase A stimulation and needs to attain a critical level in order for the cells to differentiate. (C) 2003 Elsevier B.V. All rights reserved.