CD44: a multitude of isoforms with diverse functions.

The CD44 transmembrane glycoprotein of 90 kD has been known for more than ten years under such diverse designations as lymphocyte homing receptor gp90Hermes, phagocytic glycoprotein Pgp-1, extracellular matrix receptor III (ECMRIII) and hyaluronate receptor H-CAM (see reviews by Haynes et al., 1989 and 1991). Studies with monoclonal antibodies revealed similarity, and most likely identity among these molecules (Omary et al., 1988; Gallatin et al., 1989; Picker et al., 1989; Aruffo et al., 1990; Miyake et al., 1990; Culty et al., 1990). When the human, baboon and murine cDNA sequences were established identity was confirmed. However, the cDNA sequence codes only for about 360 amino acids, revealing a just 37 kD encompassing protein core (Stamenkovic et al., 1989; Goldstein et al., 1989; Idzerda et al., 1989; Nottenburg et al., 1989; Zhou et al., 1989; Wolffe et al., 1990). This protein core is highly glycosylated by N- and O-linked sugars to yield a 85 to 90 kD form and is sometimes additionally linked to chondroitin sulfate side chains to produce a 180 - 200 kD form (Jalkanen et al., 1988; Stamenkovic et al., 1989). Concomitant with the diverse names for CD44, the description of functions was as diverse: CD44 molecules were described to participate in cell-cell and cell-matrix interactions such as lymphocyte recirculation and prothymocyte homing, hematopoiesis, lymphocyte and monocyte activation, cell migration and metastasis (reviewed in Haynes et al., 1989 and 1991). It seemed rather unlikely that all these functions were associated with one and the same molecule, though differences in the posttranslational modification may as well modulate the adhesive properties (Brown et al., 1991). Thus, the description of new extracellular regions led to the assumption that the multitude of functions may be attributed to the various isoforms (Günthert et al., 1991; Brown et al., 1991; Hofmann et al., 1991; He et al., 1992; Matsumura and Tarin, 1992). The aim of this review article is to describe the ever growing family of isoforms and their organization and to discuss possible functional implications.