Identification and characterization of novel substrates of Trk receptors in developing neurons

Xiaozhong Qian, Antonella Riccio, Yuan Zhang, David D. Ginty

Research output: Contribution to journalArticlepeer-review

Abstract

Neurotrophins influence growth and survival of specific populations of neurons through activation of Trks, members of the receptor tyrosine kinase (RTK) family. In this report, we describe the identification and characterization of two substrates of Trk kinases, rAPS and SH2-B, which are closely related Src homolog 2 (SH2) domain-containing signaling molecules. rAPS and SH2-B are substrates of TrkB and TrkC in cortical neurons and SH2-B is a substrate of TrkA in sympathetic neurons. Moreover, rAPS and SH2-B bind to Grb2, and both are sufficient to mediate NGF induction of Ras, MAP kinase (MAPK), and morphological differentiation of PC12 cells. Lastly, antibody perturbation and transient transfection experiments indicate that SH2-B, or a closely related molecule, is necessary for NGF-dependent signaling in neonatal sympathetic neurons. Together, these observations indicate that rAPS and SH2-B mediate Trk signaling in developing neurons.

Original languageEnglish (US)
Pages (from-to)1017-1029
Number of pages13
JournalNeuron
Volume21
Issue number5
DOIs
StatePublished - Nov 1998

ASJC Scopus subject areas

  • Neuroscience(all)

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