Cloning and characterization of a naturally occurring soluble form of TGF-beta type I receptor.
Transforming growth factor-beta1 (TGF-beta1) has been implicated to play an important role both in the process of normal development and in the pathogenesis of a wide variety of disease processes, including those of the kidney. TGF-beta1 regulates diverse cellular functions via a heteromeric signaling complex of two transmembrane serine/threonine kinase receptors (types I and II). Several distinct type I receptors have been described and are thought to determine specificity of the TGF-beta response and confer multifunctionality. This report reveals the cloning of a novel, naturally occurring soluble form of TGF-beta type I receptor, designated sTbetaR-I, from a rat kidney cDNA library. In vivo expression of a mRNA transcript encoding the sTbetaR-I, which lacks the transmembrane and cytoplasmic domains, is confirmed by RT-PCR followed by Southern blot analysis and by RNase protection assay. The sTbetaR-I mRNA abundance is greater in the neonatal rat kidney compared with the adult rat kidney. Furthermore, sTbetaR-I is a functional protein capable of binding TGF-beta1 ligands in the presence of a TGF-beta type II receptor on the cell surface, as determined by affinity cross-linking with 125I-labeled TGF-beta1. Studies using p3TP-Lux reporter construct reveal that this novel protein may function as a potentiator of TGF-beta signaling. The discovery of a sTbetaR-I provides an additional level of complexity to the TGF-beta receptor system.
Choi
M E
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Section of Nephrology and Department of Internal Medicine, Yale University School of Medicine and the Veterans Affairs Connecticut Healthcare Systems, New Haven, Connecticut 06520, USA.
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta