XB-ART-11821Pharmacol Ther. January 1, 2000; 20 (1): 299-311.
Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps.
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.
PubMed ID: 10594032
PMC ID: PMC85085
Article link: Pharmacol Ther.
Grant support: R01 CA49152 NCI NIH HHS , R01 DK45943 NIDDK NIH HHS , R01 DK51729 NIDDK NIH HHS , R01 DK051729 NIDDK NIH HHS , R01 DK45943 NIDDK NIH HHS , R01 CA049152 NCI NIH HHS , R01 DK51729 NIDDK NIH HHS , R01 CA49152 NCI NIH HHS , R01 DK045943 NIDDK NIH HHS
Genes referenced: mapk1 nr0b2 ptpn11