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Antibody-induced mitogenicity mediated by a chimeric CD2-c-fms receptor
M F Roussel1, C Transy, J Y Kato
1Department of Tumor Cell Biology, St. Jude Children's Research Hospitals, Memphis, Tennessee 38105.
Molecular and Cellular Biology
|May 1, 1990
Summary
Researchers created a chimeric receptor combining CD2 and CSF-1R domains. This engineered receptor triggered cell growth in fibroblasts but not in T cells, revealing insights into signal transduction.
Area of Science:
- Molecular Biology
- Cell Signaling
- Immunology
Background:
- The colony-stimulating factor 1 receptor (CSF-1R) is a tyrosine kinase receptor involved in cell proliferation and survival.
- T-cell antigen CD2 (T11) is a cell surface glycoprotein crucial for T-cell activation.
Purpose of the Study:
- To investigate the functional role of the CSF-1R kinase domain in signal transduction.
- To determine if CSF-1R can be activated independently of CSF-1 in different cellular contexts.
Main Methods:
- Creation of a chimeric receptor combining the extracellular domain of CD2 with the transmembrane and intracellular domains of CSF-1R.
- Expression of the chimeric receptor in NIH 3T3 fibroblasts.
- Stimulation of cells with anti-CD2 monoclonal antibodies.
- Analysis of receptor phosphorylation, downmodulation, and mitogenesis.
Main Results:
- Stimulation of fibroblasts expressing the chimeric receptor with anti-CD2 antibodies induced tyrosine phosphorylation, receptor downmodulation, and mitogenesis.
- The chimeric receptor and native human CSF-1R were non-functional in interleukin-2-dependent murine T cells.
- CSF-1 was not required for chimeric receptor activation or biological response in fibroblasts.
Conclusions:
- The intracellular tyrosine kinase domain of CSF-1R can mediate biological responses, such as mitogenesis, when coupled to an activating extracellular domain (CD2) in fibroblasts.
- T cells may possess intrinsic mechanisms that prevent the activation of CSF-1R or its downstream signaling pathways, irrespective of the extracellular ligand or activating domain.