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KMID : 0356619930080040422
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Journal of Korean Society of Endocrinology
1993 Volume.8 No. 4 p.422 ~ p.431
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Activation of Phosphatidylinositol 4, 5-biphosphate(PIP2) Cascade by Thyroid Stimulating Antibody
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정재훈
조보연/전재석/박경수/김성연/이홍규/고창순
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Abstract
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ABSTRACT
@EN In thyroid cells, thyrotropin (TSH) is able to activate the phosphatidylinositol 4, 5-biphosphate (PIP2) as well as cAMP cascades, whereas thyroid stimulating antibody (TSAb) stimulates only adenylyl cyclase. Recently, it has been reported
that
TSAb
can also activate PIP2 cascade in thyroid cells, but it seems that such TSAb may be restricted. To investigate whether most TSAb can activate PIP2 cascade and what were the characteristics of TSAb to stimulate it, if restricted, we studied 28
patients
with Graves' disease. In FRTL-5 cells, TSH activated both cAMP and PIP2 cascades and TSAb activated also cAMP pathway but most of them except one did not stimulate PIP2 hydrolysis. Only one TSAb stimulated total inositol phosphates (IP)
production
in
FRTL-5 cells and Cos-7 cells expressing the Mc2 and Mc4 mutant cDNA, values being 1.9, 2.1, 1.7 fold-increase over control, respectively. Moreover, the addition of phenylisopropyl adenosine (PIA) increased total IP production up to 3.3
fold-increase
over control in this case. A Graves' patient with increase of total IP formation had high TBII activities (over 90%) after radioactive iodine treatment and pretibial myxedema but the degree of goier size and hyperthyroidism were not severe. The
blocking-type TSH receptor antibodies from patients with atrophic thyroiditis inhibited TSH-or TSAb-induced total IP as well as cAMP increase regardless of the addition of PIA, but had no effect on ATP-stimulate total IP production. These
findings
suggest that the TSAb to activate PIP2 cascade may be restricted and its pathway is activated by binding to TSH receptor (J Kor Soc Endocrinol 8:422~431, 1993).
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KEYWORD
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