THE SHP-2 TYROSINE PHOSPHATASE HAS OPPOSITE EFFECTS IN MEDIATING THE ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED AND C-JUN NH2-TERMINAL MITOGEN-ACTIVATED PROTEIN-KINASES

Authors
Citation
Zq. Shi et al., THE SHP-2 TYROSINE PHOSPHATASE HAS OPPOSITE EFFECTS IN MEDIATING THE ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED AND C-JUN NH2-TERMINAL MITOGEN-ACTIVATED PROTEIN-KINASES, The Journal of biological chemistry, 273(9), 1998, pp. 4904-4908
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4904 - 4908
Database
ISI
SICI code
0021-9258(1998)273:9<4904:TSTPHO>2.0.ZU;2-7
Abstract
Shp-2 is a widely expressed cytoplasmic tyrosine phosphatase with two SH2 domains, A targeted mutant allele of the Shp-2 gene with a deletio n of 65 amino acids in the NH2-terminal SH2 domain was created that le ads to embryonic lethality at mid-gestation in homozygous mutant mice, To define the Shp-2 function in cell signaling, we have established m utant fibroblast cell lines, and have examined the effect of the Shp-2 mutation on extracellular signal-regulated kinase (ERK) and c-Jun NH2 -terminal kinase (JNK) mitogen-activated protein (MAP) kinase pathways , Insulin-like growth factor (IGF)-I-induced ERK activation was comple tely abolished, while ERK activity upon platelet-derived growth factor and epidermal growth factor stimulation was significantly reduced and shortened in mutant cells. Stimulation of ERK by phorbol la-myristate 13-acetate was not affected in mutant cells, but the phorbol 12-myris tate Is-acetate induced ERK activity decayed much faster compared with that in wild-type cells, In contrast, JNK activation upon heat shock was significantly enhanced in Shp-2 mutant cells, Based on these resul ts, we conclude that Shp-2 plays differential positive regulatory role s in various mitogenic signaling pathways leading to ERK activation, a nd that Shp-2 is a negative effector in JNK activation by cellular str ess, This is the first evidence that a tyrosine phosphatase has opposi te effects in mediating the activation of ERK and JNK MAP kinases.