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J. Biol. Chem., Vol. 276, Issue 17, 13718-13726, April 27, 2001
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From the § Department of Medicine, Division of
Gastroenterology, and the We have identified a novel basic leucine zipper
(bZIP) protein, designated ATF-7, that physically interacts with the
PRL-1 protein-tyrosine phosphatase (PTPase). PRL-1 is a predominantly nuclear, farnesylated PTPase that has been linked to the control of
cellular growth and differentiation. This interaction was initially found using the yeast two-hybrid system. ATF-7 is most closely related
to members of the ATF/CREB family of bZIP proteins, with highest
homology to ATF-4. ATF-7 homodimers can bind specifically to CRE
elements. ATF-7 is expressed in a number of different tissues and is
expressed in association with differentiation in the Caco-2 cell model
of intestinal differentiation. We have confirmed the PRL-1·ATF-7
interaction and mapped the regions of ATF-7 and PRL-1 important
for interaction to ATF-7's bZIP region and PRL-1's phosphatase domain. Finally, we have determined that PRL-1 is able to
dephosphorylate ATF-7 in vitro. Further insight into
ATF-7's precise cellular roles, transcriptional function, and
downstream targets are likely be of importance in understanding the
mechanisms underlying the complex processes of maintenance,
differentiation, and turnover of epithelial tissues.
ATF-7, a Novel bZIP Protein, Interacts with the PRL-1
Protein-tyrosine Phosphatase*
,,,, and Department of Genetics,
University of Pennsylvania School of Medicine, Philadelphia,
Pennsylvania 19104-6145
*
This work is supported by National Institutes of Health
Grants R01 DK52216 and R01 DK44237, by University of Pennsylvania NIDDK/National Institutes of Health Center for Molecular Studies in
Digestive and Liver Diseases Grant P30 DK50306, and by the American
Digestive Health Foundation Miles and Shirley Fiterman Award for Basic
Science Research.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.
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