SH2-B and APS are multimeric adapters that augment TrkA signaling

X. Qian, D. D. Ginty

Research output: Contribution to journalArticle

Abstract

Neurotrophins influence growth and survival of sympathetic and sensory neurons through activation of their receptors, Trk receptor tyrosine kinases. Previously, we identified Src homology 2-B (SH2-B) and APS, which are structurally similar adapter proteins, as substrates of Trk kinases. In the present study, we demonstrate that both SH2-B and APS exist in cells as homopentamers and/or heteropentamers, independent of Trk receptor activation. Structure-function analyses revealed that the SH2-B multimerization domain resides within its amino terminus, which is necessary for SH2-B-mediated nerve growth factor (NGF) signaling. Overexpression of SH2-B enhances both the magnitude and duration of TrkA autophosphorylation following exposure of PC12 cells to NGF, and this effect requires the amino-terminal multimerization motif. Moreover, the amino terminus of SH2-B is necessary for TrkA/SH2-B-mediated morphological differentiation of PC12 cells. Together, these results indicate that the multimeric adapters SH2-B and APS influence neurotrophin signaling through direct modulation of Trk receptor autophosphorylation.

Original languageEnglish (US)
Pages (from-to)1613-1620
Number of pages8
JournalMolecular and Cellular Biology
Volume21
Issue number5
DOIs
Publication statusPublished - 2001

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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