Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a positive regulatory role.
J Immunol
; 160(10): 4657-61, 1998 May 15.
Article
in En
| MEDLINE
| ID: mdl-9590209
ABSTRACT
Binding of IL-2 to its receptor activates several biochemical pathways, but precisely how these pathways are linked is incompletely understood. Here, we report that SHP-2, an SH2-domain containing tyrosine phosphatase, associates with different molecules of the IL-2 signaling cascade. Upon IL-2 stimulation, SHP-2 was coimmunoprecipitated with Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. In contrast, SHP-2 was constitutively associated with JAK1 and JAK3. Finally, SHP-2 expression amplified STAT-dependent transcriptional activation whereas a dominant negative allele inhibited transactivation and the IL-2-induced activation of MAPK (mitogen-activated protein kinase). These results demonstrate the involvement of SHP-2 in multiple pathways of the IL-2 signaling cascade and provide evidence for its positive regulatory role.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-2
/
Protein Tyrosine Phosphatases
/
Adaptor Proteins, Signal Transducing
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
1998
Document type:
Article
Affiliation country:
Estados Unidos