SHP-2 is involved in neurotrophin signaling.

To investigate the involvement of SHP-2 in the signal transduction pathway stimulated by neurotrophins, the association of SHP-2 with components of the pathway was examined. Following NGF stimulation of PC12 cells, SHP-2 was found to be associated with the p85 subunit of PI3-kinase and the Shc proteins. In retinoic acid-differentiated SH-SY5Y cells and primary cultures of rat cortical neurons, BDNF treatment similarly caused the association of SHP-2 with p85. In addition, a tyrosine-phosphorylated protein, which is probably TrkB, was coimmunoprecipitated with SHP-2 in both cultures. These results show that SHP-2 becomes associated with signaling proteins after treatment with neurotrophins and suggest that SHP-2 plays a fundamental role in neurotrophin signaling.