CD44 cell adhesion molecules

The CD44 proteins form a ubiquitously expressed family of cell surface adhe sion molecules involved in cell-cell and cell-matrix interactions. The mult iple protein isoforms are encoded by a single gene by alternative splicing and are further modified by a range of post-translational modifications. CD 44 proteins are single chain molecules comprising an N-terminal extracellul ar domain, a membrane proximal region, a transmembrane domain, and a cytopl asmic tail. The CD44 gene has only been detected in higher organisms and th e amino acid sequence of most of the molecule is highly conserved between m ammalian species. The principal ligand of CD44 is hyaluronic acid, an integ ral component of the extracellular matrix. Other CD44 ligands include osteo pontin, serglycin, collagens, fibronectin, and laminin. The major physiolog ical role of CD44 is to maintain organ and tissue structure via cell-cell a nd cell-matrix adhesion, but certain variant isoforms can also mediate lymp hocyte activation and homing, and the presentation of chemical factors and hormones. Increased interest has been directed at the characterisation of t his molecule since it was observed that expression of multiple CD44 isoform s is greatly upregulated in neoplasia. CD44, particularly its variants, may be useful as a diagnostic or prognostic marker of malignancy and, in at le ast some human cancers, it may be a potential target for cancer therapy. Th is review describes the structure of the CD44 gene and discusses some of it s roles in physiological and pathological processes.