Cloning and characterization of a naturally occurring soluble
form.
Choi, Mary E.
Section of Nephrology and Department of Internal Medicine, Yale
University School of Medicine and the VA Connecticut Healthcare
Systems, New Haven, Connecticut 06520
APStracts 5:0186F, 1998.
Transforming growth factor-[beta]1 (TGF-[beta]1) 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 the kidney. TGF-[beta]1 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 sT[beta]R-I,
from a rat kidney cDNA library. In vivo expression of a mRNA
transcript encoding the sT[beta]R-I, which lacks the transmembrane
and cytoplasmic domains, is confirmed by reverse transcription
-polymerase chain reaction followed by Southern blot analysis, and by
RNase protection assay. The sT[beta]R-I mRNA abundance is greater in
the neonatal rat kidney compared to the adult rat kidney.
Furthermore, the sT[beta]R-I is a functional protein capable of
binding TGF-[beta]1 ligand in the presence of TGF-[beta] type II
receptor on the cell surface, as determined by affinity cross-linking
with 125I-labeled TGF-[beta]1. Studies using p3TP-Lux reporter
construct reveal that this novel protein may function as a
potentiator of TGF-[beta] signaling. The discovery of a sT[beta]R-I
provides an additional level of complexity to the TGF-[beta] receptor
system.
Received 18 August 1998; accepted in final form 8 October 1998.
APS Manuscript Number F212-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998