Cloning and characterization of a naturally occurring soluble form of TGF-beta type I receptor

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 pat hogenesis of a wide variety of disease processes, including those of the ki dney. TGF-beta 1 regulates diverse cellular functions via a heteromeric sig naling complex of two transmembrane serine/threonine kinase receptors (type s I and II). Several distinct type I receptors have been described and are thought to determine specificity of the TGF-beta response and confer multif unctionality. This report reveals the cloning of a novel, naturally occurri ng 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 RT-PCR followed by Southern blot analysis and by RNase protect ion assay. The sT beta R-I mRNA abundance is greater in the neonatal rat ki dney compared with the adult rat kidney. Furthermore, sT beta R-I is a func tional protein capable of binding TGF-beta 1 ligands in the presence of a T GF-beta type II receptor on the cell surface, as determined by affinity cro ss-linking with I-125-labeled TGF-beta 1. Studies using p3TP-Lux reporter c onstruct reveal that this novel protein may function as a potentiator of TG F-beta signaling. The discovery of a sT beta R-I provides an additional lev el of complexity to the TGF-beta receptor system.