Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors

Blood. 1999 Mar 15;93(6):1809-16.

Abstract

We previously found that the adapter protein Gab1 (110 kD) is tyrosine-phosphorylated and forms a complex with SHP-2 and PI-3 kinase upon stimulation through either the interleukin-3 receptor (IL-3R) or gp130, the common receptor subunit of IL-6-family cytokines. In this report, we identified another adapter molecule (100 kD) interacting with SHP-2 and PI-3 kinase in response to various stimuli. The molecule displays striking homology to Gab1 at the amino acid level; thus, we named it Gab2. It contains a PH domain, proline-rich sequences, and tyrosine residues that bind to SH2 domains when they are phosphorylated. Gab1 is phosphorylated on tyrosine upon stimulation through the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors (TCR and BCR, respectively), in addition to IL-3R and gp130. Tyrosine phosphorylation of Gab2 was induced by stimulation through gp130, IL-2R, IL-3R, TPOR, SCFR, and TCR. Gab1 and Gab2 were shown to be substrates for SHP-2 in vitro. Overexpression of Gab2 enhanced the gp130 or Src-related kinases-mediated ERK2 activation as that of Gab1 did. These data indicate that Gab-family molecules act as adapters for transmitting various signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Antigens, CD / physiology
  • Cell Line
  • Cytokine Receptor gp130
  • Gene Expression
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / physiology
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-kit / physiology
  • Receptors, Antigen, B-Cell / physiology
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Cytokine*
  • Receptors, Interleukin-3 / physiology
  • Receptors, Thrombopoietin
  • Signal Transduction
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • GAB2 protein, human
  • Gab1 protein, mouse
  • Gab2 protein, mouse
  • IL6ST protein, human
  • Il6st protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Receptors, Cytokine
  • Receptors, Interleukin-3
  • Receptors, Thrombopoietin
  • Cytokine Receptor gp130
  • MPL protein, human
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-kit
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse

Associated data

  • GENBANK/AB018413
  • GENBANK/AB018414