Colony-Stimulating Factor 1–Induced STAT1 and STAT3 Activation Is Accompanied by Phosphorylation of Tyk2 in Macrophages and Tyk2 and JAK1 in Fibroblasts

• Published in: Blood 1995-10, Vol.86 (8), p.2948-2956
• Main Authors: Novak, Ulrike, Harpur, Ailsa G., Paradiso, Lucy, Kanagasundaram, Varuni, Jaworowski, Anthony, Wilks, Andrew F., Hamilton, John A.
• Format: Article
• Language: English
• Subjects: 3T3 Cells - drug effects; 3T3 Cells - metabolism; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow Cells; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; DNA-Binding Proteins - metabolism; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Interferon-beta - pharmacology; Interferon-gamma - pharmacology; Janus Kinase 1; Macrophage Colony-Stimulating Factor - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Mice; Molecular and cellular biology; Molecular Sequence Data; Phosphorylation - drug effects; Platelet-Derived Growth Factor - pharmacology; Protein Processing, Post-Translational - drug effects; Protein-Tyrosine Kinases - metabolism; Proteins - metabolism; Receptor, Macrophage Colony-Stimulating Factor - drug effects; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptor, Macrophage Colony-Stimulating Factor - metabolism; Recombinant Proteins; STAT1 Transcription Factor; STAT3 Transcription Factor; Trans-Activators - metabolism; TYK2 Kinase
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.8.2948.2948

Colony-stimulating factor 1 (CSF-1) causes the activation of STAT1 and STAT3 transcription factors in bone marrow macrophages (BMM), in the macrophage cell line BAC1.2F5, and in fibroblasts that express the wild-type receptor for CSF-1. Fibroblasts expressing a mutant receptor in which the tyrosine 809 is replaced with phenylalanine do not activate STAT proteins in response to CSF-1. The activation of the STAT proteins in BMM is accompanied by tyrosine phosphorylation of Tyk2. In fibroblasts, the activation of the STAT proteins is accompanied by tyrosine phosphorylation of Tyk2 and JAK1. We propose that these JAK kinases are subjected to very rapid phosphorylation in response to CSF-1, followed by rapid dephosphorylation. Furthermore, we propose that kinases other than JAK kinases may be involved in the phosphorylation of the STAT proteins in response to CSF-1.