Lymphotoxin-α(LT-α) is a member of the tumor necrosis factor (TNF) superfamily of proteins. It does not contain the transmembrane region and is produced as soluble trimmers. Just like the soluble TNF-α, homotrimeric LT-α3 interacts with both TNFR1 and TNFR2 and exhibits a TNF-like antitumor activity.
Interacting protein(s): TNFR1 (P7020F), TNFR2 (P7022F), HVEM (P7076F)
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|Mol. Wt. (Calculated):||18,783 daltons|
|Mol. Wt. (SDS-PAGE):||20 kd|
|Abs 0.1% (= 1 mg/ml):||1.22|
Lymphotoxin-α(LT-α) is a member of the tumor necrosis factor (TNF) superfamily of proteins. It does not contain the transmembrane region and is produced as soluble trimmers. Just like the soluble TNF-α, homotrimeric LT-α3 interacts with both TNFR1 and TNFR2 and exhibits a TNF-like antitumor activity. Thus, LT-α3 is essentially a TNF-like activity produced by lymphocytes, rather than by macrophages or neutrophils. In addition to the homotrimeric LT-α3, LTα can also complex with LT-β and form membrane anchored heterotrimeric LT-α1β2. In fact, surface expression of LT-α requires it to be complexed with the LT-α.
The LT-α1β2 interacts with LTβR and is critical for the development of lymph nodes and Peyer’s patches during embryogenesis and is indispensable for the maintenance of the structure of secondary lymphoid organs, such as spleen and the nasopharyngeal associated lymphoid tissue. In addition to its role in the organogenesis of the secondary lymphoid tissues, the lymphotoxin-LTβR axis also has been implicated for promoting tumor growth. Thus, therapeutics blocking signaling mediated by LTβR is under intensive study for cancer treatment.
Amino Acid Sequence
1. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Gray P.W., Aggarwal B.B., Benton C.V., Bringman T.S., Henzel W.J., Jarrett J.A., Leung D.W., Moffat B., Ng P., Svedersky L.P., Palladino M.A., Nedwin G.E. Nature 312:721-724 (1984)
2. The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution. Eck M.J., Ultsch M., Rinderknecht E., de Vos A.M., Sprang S.R. J. Biol. Chem. 267:2119-2122 (1992)
3. Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Alcaies A., Alter A., Antoni G., Orlova M., Nguyen V.T., Singh M., Vanderborght P.R., Katoch K., Mira M.T., Vu H.T., Ngyuen T.H., Nguyen N.B., Moraes M., Mehra N., Schurr E., Abel L. Nat. Genet. 39:517-522 (2007)