Molecular characterization and modular analysis of human MyD88.
MyD88 was first characterized as a myeloid differentiation primary response gene in mice, activated in M1 myeloleukemic cells following interleukin-6 (IL-6) induced growth arrest and terminal differentiation. Analysis of expressed sequence tags (ESTs) from activated dendritic cell libraries led to the indentification of cDNAs encoding the human homolog (hMyD88). The original description of MyD88 as a 243 aa protein may reflect a truncated mouse cDNA since the 2682 nt hMyD88 cDNA predicts a 296 aa cytoplasmic protein. Consistent with this proposal is the detection of a 33 kDa protein in human heart, kidney and liver tissue. The expression pattern of MyD88 is also more widespread than originally believed: a 2.6 kb hMyD88 mRNA species was found to be constitutively expressed in many adult human tissues; in addition MyD88 expression was observed in monocyte, T, B, NK and dendritic cells. The MyD88 protein has a modular structure composed of an N-terminal 'death domain' (DD) similar to the intracellular segments of TNF receptor 1 (TNFR1) and FAS and a C-terminal region related to the signaling domains of vertebrate interleukin-1 receptors (IL-1R) and the Drosophila morphogen Toll. This intriguing structural framework may endow MyD88 with unique signaling capabilities.
Hardiman
G
G
Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304-1104, USA.
Rock
F L
FL
Balasubramanian
S
S
Kastelein
R A
RA
Bazan
J F
JF
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000943:Antigens, Differentiation; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics*; D003713:Dendritic Cells / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011971:Receptors, Immunologic; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D018076:DNA, Complementary; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011506:Proteins; D011971:Receptors, Immunologic