Role of protein-tyrosine phosphatases on beta-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-tyrosine 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.
Division of Neurobiology, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, 700032 Calcutta, India.
Kusumika
K
Gharami
Sumantra
S
Das
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; D019833:Genistein; D017868:Cyclic AMP-Dependent Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide