- Name George Stark ; Ian Kerr
- Institute Cancer Research UK, London Research Institute: Lincoln's Inn Fields
- Tool name: 2C4-Gamma2A cell line
- Tool type: Cell Lines
- Tool sub-type: Continuous
- Parental cell line: 2C4 cell line (a derivative of HT 1080 cell line)
- Organism: Human
- Cancer type: Fibrosarcoma
- Disease: Cancer
- Model: Mutant
- Description: Mutant gamma2A cells retain a wild-type interferon (IFN)-alpha/beta response (e.g., class I HLA Binding of IFN-gamma to gamma2A cells is normal), but the cells lack detectable JAK2 mRNA and protein and are completely defective in all aspects of the IFN-gamma response. More specifically, they are defective in IFN-gamma inducible activation of the JAK/STAT pathway, gene expression, and an antiviral state with respect to encephalomyocarditis (EMC) virus. In all cases, JAK2 (but not JAK1 or Tyk2 restores a wild-type phenotype. The gamma2A mutant cells lack inducible phosphorylation of the IFN-gamma receptor 1 (R1) subunit, JAK1, and STAT1 and IFN-gamma-inducible cell surface expression of class I and II HLAs. In each case, the wild-type IFN-gamma response is restored in gamma2A/JAK2 transfectants (Kohlhuber et al., 1997).
- Research area: Cell Signaling & Signal Transduction; Gene Expression; Immunology
- Production details: The 2C4-gamma2A cell line is a derivative of the 2C4 cell line which is a clonal derivative of the human fibrosarcoma cell line HT 1080. The 2C4 cell line clone expresses the simple cell-surface marker CD2 (normally expressed only on T cells) under the control of the 9-27 gene promoter. The 9-27 gene promoter is inducible by interferon gamma; fluorescence-activated cell sorter (FACS) analysis was used to screen cells for loss or gain of interferon gamma inducibility of CD2 expression. Cell line 2C4-gamma2A was isolated by mutagenesis of 2C4 and rounds of sorting showing interferon gamma responsiveness (interferon gamma induction of CD2 expression) had been lost in comparison to wild-type 2C4 cells (Watling et al., 1993).
- For Research Use Only
- • Kohlhuber et al. 1997. Mol Cell Biol. 17(2):695-706. PMID: 9001223.
- • A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses.
- • Watling et al. 1993. Nature. 366(6451):166-70. PMID: 7901766.
- • Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-gamma signal transduction pathway.