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Molecular and Cellular Biology, January 2000, p. 299-311, Vol. 20, No. 1
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

Alana M. O'Reilly,1 Scott Pluskey,2 Steven E. Shoelson,2 and Benjamin G. Neel1,*

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.

* 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.

Molecular and Cellular Biology, January 2000, p. 299-311, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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