Tyrosine residues in the granulocyte colony-stimulating factor (G-CSF) receptor mediate G-CSF induced differentiation of murine myeloid leukemic (M1) cells
- Author(s)
- Nicholson, SE; Starr, R; Novak, U; Hilton, DJ; Layton, JE;
- Details
- Publication Year 1996-10-25,Volume 271,Issue #43,Page 26947-26953
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- The cytoplasmic tyrosine residues of many growth factor receptors have been shown to be important for receptor signal transduction via the recruitment of proteins containing phosphotyrosine-binding domains. This study demonstrates the importance of specific tyrosine residues in the granulocyte colony-stimulating factor (G-CSF) receptor cytoplasmic domain in G-CSF-induced macrophage cell differentiation. Site-directed mutagenesis was used to generate a series of G-CSF receptor (G-CSF-R) mutants in which the tyrosine residues were replaced with phenylalanine either singly or in combination, The mouse myeloid leukemic cell line (M1) transfected with G-CSF-R cDNA can be induced to differentiate into macrophages in response to G-CSF. The effect of the tyrosine mutations on this differentiation response was assessed by examining cell morphology and differentiation in soft agar colony assays. Although three of the four cytoplasmic tyrosine residues appeared to contribute to the differentiation response, mutation of a single residue (Tyr(744)) significantly reduced the ability of the M1 cells to differentiate. The STAT family of signaling molecules (Stat1, Stat3, and Stat5) were activated by G-CSF in M1 cells expressing those G-CSF-R tyrosine mutants unable to mediate G-CSF-induced differentiation. Furthermore, activation of STAT proteins was shown to occur in the absence of all four cytoplasmic tyrosine residues, suggesting an alternative mechanism for STAT activation other than direct interaction with receptor phosphotyrosines.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- GROWTH-HORMONE RECEPTOR; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; CYTOKINE RECEPTORS; KINASE JAK1; ACTIVATION; BINDING; PHOSPHORYLATION; PROLIFERATION
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- Refer to copyright notice on published article.
Creation Date: 1996-10-25 12:00:00