A discoidin domain receptor 1/SHP-2 signaling complex inhibits α2β1-integrin-mediated signal transducers and activators of transcription 1/3 activation and cell migration

Chau Zen Wang, Hsiao Wen Su, Yu Chih Hsu, Meng Ru Shen, Ming Jer Tang

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

Regulation of cell migration is an important step for the development of branching tubule morphogenesis in collagen gel. Here, we showed that discoidin domain receptor (DDR) 1a/b inhibited collagen-induced tyrosine phosphorylation of signal transducers and activators of transcription (Stat) 1/3 and cell migration triggered by α2β1-integrin. Overexpression of DDR1a/b increased the interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity of SHP-2. Expression of catalytically inactive SHP-2 in DDR1-transfected cells restored the tyrosine phosphorylation of Stat3 and cell migration. We demonstrated that the Src homology-2 (SH2)-SH2 and phosphotyrosyl phosphatase (PTP) domains of SHP-2 were responsible for interaction with DDR1 and that both tyrosine phosphorylation sites 703 and 796 of DDR1 were essential for it to bind with SHP-2. Mutation of tyrosine 703 or 796 of DDR1 abolished the ability of DDR1 to inhibit the tyrosine phosphorylation of Stat1 and Stat3 and restored collagen-induced cell migration and hepatocyte growth factor-induced branching tubulogenesis in collagen gel. Together, these results demonstrate that SHP-2 is required for the DDR1-induced suppression of Stat1 and Stat3 tyrosine phosphorylation, cell migration, and branching tubulogenesis.

Original languageEnglish
Pages (from-to)2839-2852
Number of pages14
JournalMolecular Biology of the Cell
Volume17
Issue number6
DOIs
Publication statusPublished - 2006 Jun

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A discoidin domain receptor 1/SHP-2 signaling complex inhibits α2β1-integrin-mediated signal transducers and activators of transcription 1/3 activation and cell migration'. Together they form a unique fingerprint.

Cite this