Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

Fas and TNF-R1 are cysteine-rich cell surface receptors related to the low-affinity nerve growth factor receptor family. Engagement of these receptors by their respective ligands, FasL and tumor necrosis factor, leads to apoptosis that is signaled through a conserved intracellular portion of the receptor termed the "death domain." We have cloned a new member of this family, lymphocyte-associated receptor of death (LARD), which leads to spontaneous apoptosis when expressed in 293T cells. The expression of LARD is more tightly regulated than that of either Fas or TNF-R1 as it is found predominantly on lymphocytes (T and B cells) but not on macrophages or a number of transformed lymphocyte cell lines. Alternative pre-mRNA splicing generates at least 11 distinct isoforms of LARD. The full-length isoform, LARD-1, extends to include the transmembrane and death domains, whereas the other isoforms encode potentially secreted molecules. Naive B and T cells express very little LARD-1 but express combinations of the other isoforms. Upon T cell activation, a programmed change in alternative splicing occurs so that the full-length, membrane-bound LARD-1 predominates. This may have implications for the control of lymphocyte proliferation following activation.

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

29/04/1997

Volume

94

Pages

4615 - 4619

Keywords

Alternative Splicing, Amino Acid Sequence, Apoptosis, Cloning, Molecular, Gene Expression, HeLa Cells, Humans, Lymphocytes, Lymphoid Tissue, Molecular Sequence Data, RNA Precursors, RNA, Messenger, Receptors, Nerve Growth Factor, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Member 25, Recombinant Proteins, Sequence Analysis, DNA, Sequence Homology, Amino Acid