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Molecular and Cellular Biology, January 2000, p. 299-311, Vol. 20, No. 1
Cancer Biology Program, Division of
Hematology-Oncology, Department of Medicine, Beth Israel-Deaconess
Medical Center and Harvard Medical School,1 and
Joslin Diabetes Center and Department of Medicine, Brigham
and Women's Hospital, Harvard Medical
School,2 Boston, Massachusetts
Received 12 July 1999/Returned for modification 9 August
1999/Accepted 1 September 1999
In Xenopus ectodermal explants (animal caps),
fibroblast growth factor (FGF) evokes two major events: induction of
ventrolateral mesodermal tissues and elongation. The
Xenopus FGF receptor (XFGFR) and certain downstream
components of the XFGFR signal transduction pathway (e.g., members of
the Ras/Raf/MEK/mitogen-activated protein kinase [MAPK] cascade) are
required for both of these processes. Likewise, activated versions of
these signaling components induce mesoderm and promote animal cap
elongation. Previously, using a dominant negative mutant approach, we
showed that the protein-tyrosine phosphatase SHP-2 is necessary for
FGF-induced MAPK activation, mesoderm induction, and elongation of
animal caps. Taking advantage of recent structural information, we now
have generated novel, activated mutants of SHP-2. Here, we show that
expression of these mutants induces animal cap elongation to an extent
comparable to that evoked by FGF. Surprisingly, however, activated
mutant-induced elongation can occur without mesodermal
cytodifferentiation and is accompanied by minimal activation of the
MAPK pathway and mesodermal marker expression. Our results implicate
SHP-2 in a pathway(s) directing cell movements in vivo and identify
potential downstream components of this pathway. Our activated mutants
also may be useful for determining the specific functions of SHP-2 in
other signaling systems.
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Activated Mutants of SHP-2 Preferentially Induce
Elongation of Xenopus Animal Caps
*
Corresponding author. Mailing address: HIM 1047, Beth
Israel-Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-2823. Fax: (617) 667-0610. E-mail:
bneel{at}caregroup.harvard.edu.
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