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

Parks WT, Frank DB, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker MP, McNally JG, Reddi A, Taylor SI, Roberts AB, Wang T, Lechleider RJ
J Biol Chem. 2001 276 (22): 19332-9

PMID: 11279102 · DOI:10.1074/jbc.M100606200

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-beta 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 TbetaRII. Of the type I receptors, SNX6 was found to interact only with inactivated TbetaRI. SNXs 1-4 also interacted with the transforming growth factor-beta 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.

MeSH Terms (26)

Amino Acid Sequence Animals Blotting, Western Carrier Proteins Cell Line Cloning, Molecular COS Cells Epitopes Fluorescent Antibody Technique, Indirect Humans Ligands Luciferases Molecular Sequence Data Precipitin Tests Protein-Serine-Threonine Kinases Protein Binding Protein Structure, Tertiary RNA, Messenger Sequence Homology, Amino Acid Signal Transduction Sorting Nexins Tissue Distribution Transfection Transforming Growth Factor beta Two-Hybrid System Techniques Vesicular Transport Proteins

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