Convergence of signaling by interleukin-3, granulocyte-macrophage colony-stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase
Autor: | M F, Brizzi, M G, Zini, M G, Aronica, J M, Blechman, Y, Yarden, L, Pegoraro |
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Rok vydání: | 1994 |
Předmět: |
Stem Cell Factor
Molecular Sequence Data Granulocyte-Macrophage Colony-Stimulating Factor Receptor Protein-Tyrosine Kinases In Vitro Techniques Janus Kinase 2 Protein-Tyrosine Kinases Hematopoietic Cell Growth Factors Proto-Oncogene Proteins c-kit Proto-Oncogene Proteins Receptors Colony-Stimulating Factor Humans Tyrosine Interleukin-3 Amino Acid Sequence Peptides Phosphotyrosine Signal Transduction |
Zdroj: | The Journal of biological chemistry. 269(50) |
ISSN: | 0021-9258 |
Popis: | Mast cell growth factor (MGF) (also called stem cell factor) synergizes with several lymphokines, including interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), to promote proliferation and differentiation of certain hemopoietic progenitor cells. Although similar patterns of tyrosine-phosphorylated proteins characterize cells stimulated by MGF, IL-3, and GM-CSF, only the MGF receptor is a tyrosine kinase, and the heterodimeric receptors for IL-3 and GM-CSF share a common beta subunit that is devoid of enzymatic activity. Here we show that signaling pathways utilized by all three cytokines include the cytoplasmic tyrosine kinase JAK2. Analysis of several factor-dependent myeloid cell lines indicated that JAK2 is physically associated with the common beta subunit and with MGF receptor (c-Kit) even prior to ligand binding. However, each of the ligands induced elevated tyrosine phosphorylation of JAK2 and a consequent increase in its catalytic activity. These results demonstrate for the first time the convergence within the same myeloid cells of signaling pathways originating in two distinct lymphokine receptors and a tyrosine kinase receptor on activation of a cytoplasmic tyrosine kinase. |
Databáze: | OpenAIRE |
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