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J. Biol. Chem., Vol. 275, Issue 35, 27414-27420, September 1, 2000
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From the 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.
Intersectin, an Adaptor Protein Involved in Clathrin-mediated
Endocytosis, Activates Mitogenic Signaling Pathways*
,
,
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
*
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.
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.
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