Effect of TGF-ß RII mutation on TGF-ß signaling

Abstract

We have previously reported I170T mutation of transforming growth factor- ß receptor II (TßR-II) in human oral squamous cell carcinoma samples. To analyze the functional consequences of I170T TßR-II mutation, we performed co-immunoprecipitation of TßR-II with TßR-I and determined intracellular signaling activities of TßR-II. As a result, either wild type or I170T mutant TßR-II was coprecipitated with TßR-I, regardless of TGF-ß and both wild-type and I170T mutant TßR-II exhibited similar levels of transcriptional activities upon treatment of TGF-ß1. Moreover, I170T TßR-II localized at the cell membrane similar to wild-type TßR-II. Our data showed that I170T mutation of TßR-II does not affect the receptor oligomerization, membrane localization, and downstream signaling upon binding of TGF-ß1. Taken together, these results indicate that I170T mutation of TßR-II does not change structural or physiological characteristics of TßR-II, raising the possibility that I170T might be a new SNP of TßR-II.