SHP-2 IS INVOLVED IN NEUROTROPHIN SIGNALING

To investigate the involvement of SHP-2 in the signal transduction pat hway stimulated by neurotrophins, the association of SHP-2 with compon ents of the pathway was examined. Following NGF stimulation of PC12 ce lls, SHP-2 was found to be associated with the p85 subunit of PI3-kina se and the She proteins. In retinoic acid-differentiated SH-SY5Y cells and primary cultures of rat cortical neurons, BDNF treatment similarl y caused the association of SHP-2 with p85. In addition, a tyrosine-ph osphorylated protein, which is probably TrkB, was coimmunoprecipitated with SHP-2 in both cultures. These results show that SHP-2 becomes as sociated with signaling proteins after treatment with neurotrophins an d suggest that SHP-2 plays a fundamental role in neurotrophin signalin g. (C) 1996 Academic Press, Inc.