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Molecular and Cellular Biology, December 1998, p. 7278-7287, Vol. 18, No. 12
Diabetes Branch, National Institutes of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, Bethesda, Maryland 20892,1 and
National Biomedical Research Foundation, Washington,
D.C.2
Received 31 December 1997/Returned for modification 6 March
1998/Accepted 8 September 1998
Sorting nexin 1 (SNX1) is a protein that binds to the epidermal
growth factor (EGF) receptor and is proposed to play a role in
directing EGF receptors to lysosomes for degradation (R. C. Kurten, D. L. Cadena, and G. N. Gill, Science 272:1008-1010,
1996). We have obtained full-length cDNAs and deduced the amino acid sequences of three novel homologous proteins, which were denoted human
sorting nexins (SNX2, SNX3, and SNX4). In addition, we identified a
presumed splice variant isoform of SNX1 (SNX1A). These molecules contain a conserved domain of ~100 amino acids, which was termed the
phox homology (PX) domain. Human SNX1 (522 amino acids), SNX1A (457 amino acids), SNX2 (519 amino acids), SNX3 (162 amino acids), and SNX4
(450 amino acids) are part of a larger family of hydrophilic molecules
including proteins identified in Caenorhabditis elegans and
Saccharomyces cerevisiae. Despite their hydrophilic nature, the sorting nexins are found partially associated with cellular membranes. They are widely expressed, although the tissue distribution of each sorting nexin mRNA varies. When expressed in COS7 cells, epitope-tagged sorting nexins SNX1, SNX1A, SNX2, and SNX4
coimmunoprecipitated with receptor tyrosine kinases for EGF,
platelet-derived growth factor, and insulin. These sorting nexins also
associated with the long isoform of the leptin receptor but not with
the short and medium isoforms. Interestingly, endogenous COS7
transferrin receptors associated exclusively with SNX1 and SNX1A, while
SNX3 was not found to associate with any of the receptors studied. Our
demonstration of a large conserved family of sorting nexins that
interact with a variety of receptor types suggests that these proteins
may be involved in several stages of intracellular trafficking in
mammalian cells.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Identification of a Family of Sorting Nexin
Molecules and Characterization of Their Association with
Receptors
*
Corresponding author. Mailing address: National
Institutes of Health, Building 10, Room 8S-235A, 10 Center Dr.
MSC-1770, Bethesda, MD 20892-1770. Phone: (301) 402-1629. Fax: (301)
402-0573. E-mail: carol_haft{at}nih.gov.
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