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Volume 271, Number 30,
Issue of July 26, 1996
pp. 18243-18252
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Two Separate Functions Are Encoded by the Carboxyl-terminal
Domains of the Yeast Cyclase-associated Protein and Its Mammalian
Homologs
DIMERIZATION AND ACTIN BINDING
(Received for publication, March 12, 1996, and in revised form, April 15, 1996)
Audrey
Zelicof
,
Vladimir
Protopopov
,
Doris
David
§
,
Xue-Ying
Lin
,
Vardit
Lustgarten
§
and
Jeffrey E.
Gerst
§
From the Department of Cell Biology and Anatomy,
Mount Sinai School of Medicine, New York, New York 10029 and the
§ Department of Molecular Genetics, Weizmann Institute of
Science, Rehovot 76100, Israel
The yeast adenylyl cyclase-associated protein,
CAP, was identified as a component of the RAS-activated cyclase
complex. CAP consists of two functional domains separated by a
proline-rich region. One domain, which localizes to the amino terminus,
mediates RAS signaling through adenylyl cyclase, while a domain at the
carboxyl terminus is involved in the regulation of cell growth and
morphogenesis. Recently, the carboxyl terminus of yeast CAP was shown
to sequester actin, but whether this function has been conserved, and
is the sole function of this domain, is unclear. Here, we demonstrate
that the carboxyl-terminal domains of CAP and CAP homologs have two
separate functions. We show that carboxyl-terminals of both yeast CAP
and a mammalian CAP homolog, MCH1, bind to actin. We also show that
this domain contains a signal for dimerization, allowing both CAP and
MCH1 to form homodimers and heterodimers. The properties of actin
binding and dimerization are mediated by separate regions on the
carboxyl terminus; the last 27 amino acids of CAP being critical for
actin binding. Finally, we present evidence that links a segment of the
proline-rich region of CAP to its localization in yeast. Together,
these results suggest that all three domains of CAP proteins are
functional.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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