Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases.

DOI Web Site 被引用文献6件
  • S J Corey
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA.
  • A L Burkhardt
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA.
  • J B Bolen
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA.
  • R L Geahlen
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA.
  • L S Tkatch
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA.
  • D J Tweardy
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA.

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<jats:p>Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that critically regulates the viability, proliferation, and differentiation of granulocytic precursors and the function of neutrophils by signaling through its receptor. Cloning of the human G-CSF receptor (G-CSFR) cDNA has demonstrated sequence homology with other members of the hematopoietic/cytokine receptor superfamily. G-CSF stimulates the appearance of phosphotyrosine proteins in several types of human and murine myeloid cells. Since the receptor does not possess intrinsic tyrosine kinase activity, we hypothesized that G-CSFR interacts with and activates cytosolic protein-tyrosine kinases (PTKs). In vitro protein kinase assay of human G-CSFR immunoprecipitates demonstrated at least two tyrosine phosphoproteins, pp55 and pp70. We observed that G-CSF activated p53/p56lyn, a Src-related PTK, and p72syk, a non-Src-related PTK. Lyn and Syk were recovered in anti-G-CSFR immunoprecipitates; Lyn was detected in the absence of ligand. In addition, upon G-CSF stimulation, Lyn coimmunoprecipitated with Syk. Analysis of the G-CSFR amino acid sequence revealed a potential receptor activation motif for Syk. On the basis of immunoprecipitation and sequence analysis data, we propose that the human G-CSFR forms a three-component signaling complex with Lyn and Syk. Their sequential recruitment into the G-CSFR signaling complex demonstrates the coordinated involvement of two PTKs with a member of the hematopoietic/cytokine receptor superfamily.</jats:p>

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