Ｔｒａｎｓｆｏｒｍｉｎｇ　Ｇｒｏｗｔｈ　Ｆａｃｔｏｒ‐β　Ｉ型受容体の機能解析

DOI PubMed 参考文献40件
  • 齋藤 正夫
    東京医科歯科大学大学院生体機能制御歯科学系顎顔面外科学講座

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  • Functional Analysis of Transforming Growth Factor-.BETA. Type I Receptor.

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Proteins in the transforming growth factor-β (TGF-β) superfamily exert their effects by forming heteromeric complexes of their type I and type II serine/threonine kinase receptors. Binding of TGF-β to its constitutively active type II receptor (TβR-II) recruits the type I receptor (TβR-I) into the complex ; TβR- I is thereafter phosphorylated in GS domain located just N-terminal to the kinase domain and activated, which is necessary for TGF-β signaling.<BR>Here we investigated the role of cytoplasmic juxtamembrane region located between the transmembrane domain and the GS domain of TβR-I by mutational analyses using mutant lung epithelial cells which lack endogenous TβR-I. Upon transfection, wild-type TβR-I restored the TGF-β signals for growth inhibition and production of plasminogen activator inhibitor 1 (PAI) -1 and fibronectin. A deletion-mutant, TβR-I /JD1 (Δ150-181), which lacks the juxtamembrane region preceding the GS domain bound TGF-β in concert with TβR-II and transduced a signal leading to production of PAI-1 but not growth inhibition. Recombinant receptors with mutations that change serine172 to alanine (S172A) or threonine176 to valine (T176V) were similar to wild-type TβR-I in their abilities to bind TGF-β, formed complexes with TβR-II, and transduced a signal for PAT-1 and fibronectin. Similar to TβR- I /JD1 (Δ150-181), however, these missense mutant receptors were impaired to mediate a growth inhibitory signal. These observations indicate that serine172 and threonine176 of TβR-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-β

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