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The following cytokines can be grouped into a family on the basis of
sequence, functional, and structural similarities [1,2,3]:
Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-α) [4,5]
is a cytokine which has a wide variety of functions. It can cause cytolysis
of certain tumor cell lines; it is involved in the induction of cachexia;
it is a potent pyrogen, causing fever by direct action or by stimulation of
interleukin-1 secretion; finally, it can stimulate cell proliferation
and induce cell differentiation under certain conditions.
Lymphotoxin-α (LT-α) and lymphotoxin-β (LT-β), two related
cytokines produced by lymphocytes and which are cytotoxic for a wide range
of tumor cells in vitro and in vivo .
T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-
cell development and activation.
CD27L, a cytokine which plays a role in T-cell activation. It induces the
proliferation of costimulated T cells and enhances the generation of
cytolytic T cells.
CD30L, a cytokine which induces proliferation of T cells.
4-1BBL, a inducible T cell surface molecule that contributes to T-cell
OX40L, a cytokine that co-stimulates T cell proliferation and cytokine
TNF-related apoptosis inducing ligand (TRAIL) , a cytokine that induces
TNF-α is synthesized as a type II membrane protein which then undergoes
post-translational cleavage liberating the extracellular domain. CD27L, CD30L,
CD40L, FASL, LT-β, 4-1BBL and TRAIL also appear to be type II membrane
proteins. LT-α is a secreted protein. All these cytokines seem to form
homotrimeric (or heterotrimeric in the case of LT-α/β) complexes that
are recognized by their specific receptors.
As a signature for this family of proteins, we have selected the most
conserved region. This region is located in a β-strand in the central
section of these proteins.
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
Peitsch M.C., Jongeneel C.V.
A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors.
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