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 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.
Laboratory of Cell Regulation and Carcinogenesis, NCI, the Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
W T
WT
Parks
D B
DB
Frank
C
C
Huff
C
C
Renfrew Haft
J
J
Martin
X
X
Meng
M P
MP
de Caestecker
J G
JG
McNally
A
A
Reddi
S I
SI
Taylor
A B
AB
Roberts
T
T
Wang
R J
RJ
Lechleider
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D000939:Epitopes; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D058305:Sorting Nexins; D014018:Tissue Distribution; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000737:chemistry*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D000939:Epitopes; D008024:Ligands; D012333:RNA, Messenger; C431150:SNX6 protein, human; D058305:Sorting Nexins; D016212:Transforming Growth Factor beta; D033921:Vesicular Transport Proteins; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases