Sorting Nexin 6, a Novel SNX, Interacts with the Transforming Growth Factor-β Family of Receptor Serine-Threonine Kinases

W. Tony Parks, David B. Frank, Carla Huff, Carol Renfrew Haft, Jennifer Martin, Xianwang Meng, Mark P. De Caestecker, James G. McNally, Amit Reddi, Simeon I. Taylor, Anita B. Roberts, Tongwen Wang, Robert J. Lechleider

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with members of the transforming growth factor-β family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, 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 TβRII. Of the type I receptors, SNX6 was found to interact only with inactivated TβRI. SNXs 1-4 also interacted with the transforming growth factor-β receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases.

Original languageEnglish (US)
Pages (from-to)19332-19339
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number22
DOIs
StatePublished - Jun 1 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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