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Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase
Open accessAbstract
Phosphatidylinositol 3-kinases (PI 3-kinases) have been implicated in membrane trafficking in the secretory and endocytic pathways of yeast and mammalian cells, but the molecular mechanisms by which these lipid kinases operate are not known. Here we identify a protein of 170 kDa that is rapidly released from cell membranes in response to wortmannin, a potent inhibitor of mammalian PI 3-kinases. The amino acid sequence of peptides from p170 reveal its identity to early endosomal antigen (EEA) 1, an endosomal antigen with homology to several yeast proteins genetically implicated in membrane trafficking. Immunofluorescence analysis of 3T3-L1 adipocytes with antisera against p170/EEA1 reveal a punctate peripheral pattern that becomes diffuse in response to wortmannin. In vitro , p170/EEA1 binds specifically to liposomes containing PIns(3)P, suggesting that the effect of wortmannin on cells is due to inhibition of PIns(3)P production. Thus, p170/EEA1 may define a family of proteins that mediate the regulatory effects of 3′-phosphoinositides on membrane trafficking in yeast and mammalian cells.
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Cited by
EEA1 links PI(3)K function to Rab5 regulation of endosome fusion
Simonsen, A., Lippe, R., Christoforidis, S., Gaullier, J.-M., Brech, A., Callaghan, J., Toh, B.-H., Murphy, C., Zerial, M., & Stenmark, H. (1998) · Nature · doi:10.1038/28879 · Cited by 1,133
Self-citationMolecular machinery for non-vesicular trafficking of ceramide
Hanada, K., Kumagai, K., Yasuda, S., Miura, Y., Kawano, M., Fukasawa, M., & Nishijima, M. (2003) · Nature · doi:10.1038/nature02188 · Cited by 1,051
Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells
Gillooly, D. J., Morrow, I. C., Lindsay, M., Gould, R., Bryant, N. J., Gaullier, J., Parton, R. G., & Stenmark, H. (2000) · The EMBO Journal · doi:10.1093/emboj/19.17.4577 · Cited by 1,031
Rabs and their effectors: achieving specificity in membrane traffic
Grosshans, B. L., Ortiz, D., & Novick, P. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601617103 · Cited by 1,005
The Role of Phosphoinositide 3-Kinase Lipid Products in Cell Function
Rameh, L. E., & Cantley, L. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.8347 · Cited by 987
Metadata
- Authors
- Patki, V., Virbasius, J., Lane, W. S., Toh, B.-H., Shpetner, H. S., & Corvera, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-07-08
- Volume
- 94
- Issue
- 14
- Pages
- 7326-7330
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1970909818
- Cited by
- 228
- References
- 0
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- green
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- Patki, V., Virbasius, J., Lane, W. S., Toh, B.-H., Shpetner, H. S., & Corvera, S. (1997). Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.14.7326
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