Molecular interactions of SHP1 and SHP2 in IL-3-signalling

Cell Signal. 2002 Mar;14(3):219-29. doi: 10.1016/s0898-6568(01)00241-8.

Abstract

SHP1 and SHP2 tyrosine phosphatases have both been implicated in signalling pathways downstream of the interleukin-3 (IL-3) receptor. We have investigated the co-association of SHP1 and SHP2 with tyrosine-phosphorylated proteins in IL-3-dependent BaF/3 cells. We demonstrate that both SHP1 and SHP2 associate with Aic2A (beta chain of the IL-3 receptor), Gab2 and the paired inhibitory receptor B (PIR-B). The individual SH2 domains of SHP2 can independently bind Gab2, potentially important for the adapter function of SHP2. Association of both phosphatases with Aic2A and Gab2 increases upon IL-3 treatment. Recruitment of SHP1 to PIR-B also increases in response to IL-3, suggesting a functional link between inhibitory and cytokine receptor signalling. Aic2A is a rapid target for dephosphorylation following IL-3 stimulation and substrate-trapping versions of both phosphatases identify Aic2A and Gab2 as substrates for SHP1 and SHP2. These studies suggest that SH2-domain interactions are important for targetting these phosphatases to their substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Cell Line
  • Interleukin-3 / metabolism*
  • Interleukin-3 / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptors, Immunologic / metabolism
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-3 / metabolism*
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Signal Transduction / physiology*
  • Substrate Specificity
  • src Homology Domains*

Substances

  • Adaptor Proteins, Signal Transducing
  • Gab2 protein, mouse
  • Interleukin-3
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Pirb protein, mouse
  • Receptors, Immunologic
  • Receptors, Interleukin
  • Receptors, Interleukin-3
  • interleukin 3 receptor-like molecule
  • Csf2rb2 protein, mouse
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse
  • SH2 Domain-Containing Protein Tyrosine Phosphatases