CUTTING EDGE - INVOLVEMENT OF SHP-2 IN MULTIPLE ASPECTS OF IL-2 SIGNALING - EVIDENCE FOR A POSITIVE REGULATORY ROLE

Binding of IL-2 to its receptor activates several biochemical pathways , but precisely how these pathways are linked is incompletely understo od. Here, we report that SHP-2, an SH2-domain containing tyrosine phos phatase, associates with different molecules of the IL-2 signaling cas cade, 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 ex pression amplified STAT-dependent transcriptional activation whereas a dominant negative allele inhibited transactivation and the IL-2-induc ed activation of MAPK (mitogen-activated protein kinase), These result s demonstrate the involvement of SHP-2 in multiple pathways of the IL- 2 signaling cascade and provide evidence for its positive regulatory r ole.