دورية
Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases.
العنوان: | Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases. |
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المؤلفون: | Corey, S J, Burkhardt, A L, Bolen, J B, Geahlen, R L, Tkatch, L S, Tweardy, D J |
المصدر: | Proceedings of the National Academy of Sciences of the United States of America; May 1994, Vol. 91 Issue: 11 p4683-4687, 5p |
مستخلص: | 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. |
قاعدة البيانات: | Supplemental Index |
تدمد: | 00278424 10916490 |
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DOI: | 10.1073/pnas.91.11.4683 |