Physical and Functional Interactions between Type I Transforming Growth Factor β Receptors and Bα, a WD-40 Repeat Subunit of Phosphatase 2A

ABSTRACT

We have previously shown that a WD-40 repeat protein, TRIP-1, associates with the type II transforming growth factor β (TGF-β) receptor. In this report, we show that another WD-40 repeat protein, the Bα subunit of protein phosphatase 2A, associates with the cytoplasmic domain of type I TGF-β receptors. This association depends on the kinase activity of the type I receptor, is increased by coexpression of the type II receptor, which is known to phosphorylate and activate the type I receptor, and allows the type I receptor to phosphorylate Bα. Furthermore, Bα enhances the growth inhibition activity of TGF-β in a receptor-dependent manner. Because Bα has been characterized as a regulator of phosphatase 2A activity, our observations suggest possible functional interactions between the TGF-β receptor complex and the regulation of protein phosphatase 2A.

ACKNOWLEDGMENTS

The research was sponsored by NIH grants CA63101 to R.D. and GM49505 to M.C.M., a postdoctoral training grant from the Cardiovascular Research Institute at UCSF and a postdoctoral fellowship from the American Heart Association to I.G.-P, and a postdoctoral fellowship from the American Heart Association (Texas Affiliate) to C.K.

We thank Joan Massagué for the Mv1Lu mutant cells and the 3TP-luciferase plasmid and Norbert Fusenig for HaCaT cells. We also thank Lisa Choy, Tony DeFranco, Ellen Filvaroff, and Xin-Hua Feng for critical reading of the manuscript.