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J. Biol. Chem. 275 (35): 27414-27420

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

Intersectin, an Adaptor Protein Involved in Clathrin-mediated Endocytosis, Activates Mitogenic Signaling Pathways*

Anthony AdamsDagger , Judith M. ThornDagger , Montarop Yamabhai§, Brian K. Kay§, and John P. O'BryanDagger ||

From the Dagger  Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709 and the § Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706

Intersectin is a member of a growing family of adaptor proteins that possess conserved Eps15 homology (EH) domains as well as additional protein recognition motifs. In general, EH domain-containing proteins play an integral role in clathrin-mediated endocytosis. Indeed, intersectin functions in the intermediate stages of clathrin-coated vesicle assembly. However, recent evidence suggests that components of the endocytic machinery also regulate mitogenic signaling pathways. In this report, we provide several lines of evidence that intersectin has the capacity to activate mitogenic signaling pathways. First, intersectin overexpression activated the Elk-1 transcription factor in an MAPK-independent manner. This ability resides within the EH domains, as expression of the tandem EH domains was sufficient to activate Elk-1. Second, intersectin cooperated with epidermal growth factor to potentiate Elk-1 activation; however, a similar level of Elk-1 activation was obtained by expression of the tandem EH domains suggesting that the coiled-coil region and SH3 domains act to regulate the EH domains. Third, intersectin expression was sufficient to induce oncogenic transformation of rodent fibroblasts. And finally, intersectin cooperated with progesterone to accelerate maturation of Xenopus laevis oocytes. Together, these data suggest that intersectin links endocytosis with regulation of pathways important for cell growth and differentiation.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235.

|| To whom correspondence should be addressed: National Institute of Environmental Health Sciences, National Institutes of Health, Bldg. 101, Rm. F336, MD F3-06, P.O. Box 12233, Research Triangle Park, NC 27709. Tel.: 919-541-3619; Fax: 919-541-1898; E-mail: obryan@niehs.nih.gov.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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