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

Cell Signal. 2003 Mar;15(3):319-26. doi: 10.1016/s0898-6568(02)00122-5.

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, Y(546) and Y(584). 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 (Y(546) and Y(584)). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Breast Neoplasms
  • GRB2 Adaptor Protein
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Janus Kinase 2
  • Lymphoma
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Precipitin Tests
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism
  • Proto-Oncogene Proteins*
  • Rats
  • Receptors, Prolactin / metabolism*
  • Signal Transduction / physiology*
  • Substrate Specificity
  • Tumor Cells, Cultured
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Grb2 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Prolactin
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Jak2 protein, rat
  • Janus Kinase 2
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, rat