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Molecular characterization and modular analysis of human MyD88
G Hardiman1, F L Rock, S Balasubramanian
1Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304-1104, USA.
Oncogene
|December 5, 1996
Summary
MyD88, a key immune response gene, is expressed more widely in human tissues and cells than previously known. Its modular structure suggests novel signaling roles in immunity.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Myeloid differentiation primary response gene 88 (MyD88) was initially identified in mice.
- Its role in immune cell differentiation and response to cytokines like IL-6 was suggested.
- The human homolog (hMyD88) was identified through expressed sequence tag analysis.
Purpose of the Study:
- To characterize the human homolog of MyD88 (hMyD88).
- To determine the expression pattern and protein size of hMyD88.
- To investigate the structural features and potential signaling capabilities of hMyD88.
Main Methods:
- Expressed sequence tag (EST) analysis for identifying human cDNA.
- Northern blot analysis to detect mRNA species.
- Western blot analysis to detect protein expression.
Main Results:
- Identified a 2682 nt hMyD88 cDNA predicting a 296 amino acid protein.
- Detected a 33 kDa hMyD88 protein in human tissues (heart, kidney, liver).
- Found constitutive expression of a 2.6 kb hMyD88 mRNA in various adult human tissues and immune cells (monocytes, T cells, B cells, NK cells, dendritic cells).
Conclusions:
- hMyD88 expression is more widespread than initially believed.
- hMyD88 possesses a modular structure with an N-terminal death domain and a C-terminal Toll/IL-1R-like region.
- The unique structure suggests MyD88 has significant, potentially novel, signaling functions in immune responses.