Activated T cells express a novel gene on chromosome 8 that is closely related to the murine ecotropic retroviral receptor.

Abstract

A novel cDNA clone (20.5) which is differentially expressed between two closely related T-lymphoma cell clones was isolated by subtraction-enriched differential screening. SL12.4 cells, from which the cDNA was isolated, have characteristics of thymocytes at an intermediate stage in development. A sister cell clone derived from the same tumor, SL12.3, does not express this mRNA, has a distinct phenotype, and expresses fewer genes required for mature T-cell function. The cDNA sequence predicts a highly hydrophobic protein (approximately 49.5 kilodaltons) which contains seven putative membrane spanning domains. The gene was expressed on concanavalin A-activated T lymphocytes and was designated Tea (T-cell early activation gene). The Tea gene mapped to chromosome 8 and appeared to be conserved among mammalian and avian species. The Tea gene is distinct from, but bears extensive amino acid and DNA sequence similarity with, the murine ecotropic retroviral receptor which is encoded by the Rec-1 gene. Neither gene product displayed significant homology with other known transmembrane-spanning proteins. Thus, the Tea and Rec-1 genes establish a new family encoding multiple membrane-spanning proteins.

Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.

“…Expression of this gene is increased in T cells following treatment with conconavalin A (MacLeod et al 1990;Yoshimoto et al 1992) and in B cells after treatment with lipopolysaccharide (Yoshimoto et al 1992). Elevated expression is also a consequence of treatment with phorbol 12-myristate 13-acetate (PMA) or calcium ionophore (Yoshimoto et al 1992).…”

“…Increased mCAT-1 expression has been linked to cell proliferation in a number of cases (MacLeod et al 1990;Yoshimoto et al 1992;Wu et al 1994). Expression of this gene is increased in T cells following treatment with conconavalin A (MacLeod et al 1990;Yoshimoto et al 1992) and in B cells after treatment with lipopolysaccharide (Yoshimoto et al 1992).…”

“…mCAT-1 is widely ex pressed in both the developing and adult animal, consis tent with the wide tissue tropism of the ecotropic mu rine leukemia viruses (MuLVs) and is believed to encode the major transporter of cationic amino acids in mam malian cells, the Na^-independent y^^ transporter sys tem (White 1985). mCAT2 has been shown to encode two proteins, termed mCAT-2A and mCAT-2B (MacLeod et al 1990;Closs et al 1993a,b;Kavanaugh et al 1994). The mCAT-2 proteins exhibit a more restricted expression pattern as well as transport properties differ-ent from mCAT-1.…”

“…mCAT-2A, which represents y^^, is a liver-specific transporter with a relatively low affinity for substrates (Closs et al 1993a;Kavanaugh et al 1994). mCAT-2B, which also has been called Tea (T cell early activation), has been cloned from both T-cell sources (MacLeod et al 1990;Kavanaugh et al 1994) and lipopolysaccharide-stimulated macrophages (Closs et al 1993b). This protein, which differs from mCAT-2A in a 42-amino-acid stretch, has transport properties more similar to mCAT-1.…”

Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain

“…However, circumstantial evidence suggested that CD98hc was strongly linked to amino acid transport but was not the transporter itself (Bertran et al, 1992;Macleod et al, 1994). The ®rst light chain (Lc1 or LAT1) associated with CD98hc have been identi®ed at long last (Kanai et al, 1998, Mastroberardino et al, 1998Nakamura et al, 1999;Tsurudome et al, 1999), and this molecule proved to be TA1/E16 (Sang et al, 1995).…”