Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases

Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorti ng of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been propo sed to play a role in receptor trafficking and have been shown to bind to s everal receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long for m of the leptin receptor, a glycoprotein 130-associated receptor. We now de scribe a novel member of this family, SNX6, which interacts with mem bers o f the transforming growth factor-p family of receptor serine-threonine kina ses. These receptors belong to two classes: type II receptors that bind lig and, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of T beta RII. Of the type I receptors, SNX6 was found to interact only with i nactivated T beta RI. SNXs 1-4 also interacted with the transforming growth factor-p receptor family, showing different receptor preferences. Converse ly, SNX6 behaved similarly to the other SNX proteins in its interactions wi th receptor tyrosine kinases. Strong heteromeric interactions were also see n among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeri c complexes. These findings are the first evidence for the association of t he SNX family of molecules with receptor serine-threonine kinases.