The adaptor function of SHP-2 downstream of the prolactin receptor is required for the recruitment of p29, a substrate of SHP-2

Parham Minoo, Naila Chughtai, Manuela Campiglio, Matthias Stein-Gerlach, Jean Jacques Lebrun, Axel Ullrich, Suhad Ali

Research output: Contribution to journalArticle

Abstract

SHP-2, a cytosolic protein tyrosine phosphatase with two SH2 domains and multiple tyrosine phosphorylation sites, contributes to signal transduction as an enzyme and/or adaptor molecule. Here we demonstrate that prolactin (PRL) stimulation of the PRL-responsive Nb2 cells, a rat lymphoma cell line, and T47D cells, a human breast cancer cell line, lead to the complex formation of SHP-2 and growth factor receptor-bound protein-2 (grb2). Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y546 and Y584. Furthermore, in this study, we found a highly phosphorylated, 29-kDa protein (p29), a substrate of SHP-2. The recruitment of p29 to SHP-2 requires the carboxy-terminal tyrosine residues of SHP-2 (Y546 and Y584). Together, our results indicate that SHP-2 may function as an adaptor molecule downstream of the PRLR and highlight a new recruitment mechanism of SHP-2 substrates.

Original languageEnglish
Pages (from-to)319-326
Number of pages8
JournalCellular Signalling
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

Keywords

  • Grb2
  • Jak/Stat
  • Phosphatase
  • Prolactin
  • Prolactin receptor
  • SHP-2
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'The adaptor function of SHP-2 downstream of the prolactin receptor is required for the recruitment of p29, a substrate of SHP-2'. Together they form a unique fingerprint.

  • Cite this