Inositol 1,4,5-trisphosphate 3-kinase activity in FRTL-5 cells: regulation of the enzyme activity by TSH.
Inositol 1,4,5-trisphosphate (InsP3) 3-kinase phosphorylates the Ca(2+)-mobilizing second messenger InsP3 to inositol 1,3,4,5-tetrakisphosphate (InsP4). InsP3 5-phosphatase dephosphorylates InsP3 to inositol 1,4-bisphosphate (InsP2). We compared the effects of TSH added to a culture of FRTL-5 thyroid cells on the activity of InsP3 5-phosphatase and InsP3 3-kinase. InsP3 3-kinase activity was decreased at a physiological concentration of TSH. Inhibition of this activity started after 3 h of incubation with TSH and was maximal after 24 h. In contrast, InsP3 5-phosphatase activity was not affected by TSH under the same conditions. The inhibitory effect of TSH on InsP3 3-kinase was characterized as follows: a) inhibition of activity was mimicked by both dibutyryl cyclic AMP and forskolin; b) activity obtained by mixing lysates of TSH-stimulated and non-stimulated cells was the sum of each activity measured separately; c) inhibition persisted after a crude lysate of TSH-stimulated cells had been subjected to SDS/polyacrylamide gel electrophoresis and the extraction of InsP3 3-kinase activity. The data suggest that TSH reduced the activity of InsP3 3-kinase in FRTL-5 cells either by a phosphorylation/dephosphorylation mechanism, or by affecting expression of the enzyme.
Takazawa
K
K
Third Department of Internal Medicine, University of Yamanashi Medical School, Japan.
Go
M
M
Endo
T
T
Erneux
C
C
Onaya
T
T
D000818:Animals; D002460:Cell Line; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D000072181:Inositol Polyphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology*; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors
D013972:Thyrotropin; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases