Protein kinase A linked phosphorylation mediates triiodothyronine induced actin gene expression in developing brain.
In the developing rat cerebra, triiodothyronine (T3) stimulates actin mRNA by acting predominantly at the level of transcription whereas tubulin mRNA is enhanced primarily by post-transcriptional regulation. We report here that in primary cultures of rat cerebra, the T3-induced actin gene expression is mediated by phosphorylation events. Inhibition of protein kinase A (PKA), but not of protein kinase C (PKC) or tyrosine kinase, totally blocked the induction of actin mRNA by T3. Under identical conditions, induction of tubulin mRNA by T3 was virtually unaffected by all the inhibitors. Activators of PKA, but not of PKC, potentiated the T3-induced actin gene expression, both at mRNA and protein level, by about 2-fold. In the absence of T3, neither the inhibitor nor the activator of PKA had any significant effect on this induction. The involvement of PKA in mediating the induction of actin mRNA by T3 was confirmed by transfecting primary cultures of rat cerebra with an expression vector encoding the protein kinase A inhibitor which totally abolished the induction. T3 is shown to enhance the phosphorylation of the thyroid hormone receptor, TRalpha, by about 2-fold but the level of phosphorylation of TRbeta remained virtually unaffected.
Sarkar
S
S
Division of Neurobiology, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Calcutta, 700 032, India.
Biswas
S C
SC
Chatterjee
O
O
Sarkar
P K
PK
D000199:Actins / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003599:Cytoskeleton / Q000737:chemistry / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D010766:Phosphorylation; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism*
D000199:Actins; D012333:RNA, Messenger; D014284:Triiodothyronine; D005576:Colforsin; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases