Figure 1. Schematic representation of CD44S. A: The extracellular (blue), transmembrane (red), and cytoplasmic (green) domains are illustrated for standard CD44S. The extracellular domain is characterized by cysteine residues that form disulfide bonds (maroon beads), including the two signature disulfide bonds that form the backbone of the link domain. Several extracellular putative phosphorylation sites as well as docking sites for MMP-9 and cleavages of CD44 by MT1-MMP (in conjunction with ADAMs 10 and 17) in the CD44 stem region and the transmembrane region by γ-secretase are shown. The cytoplasmic domain is characterized by three cytoplasmic phosphorylation sites (purple arrows) that modulate CD44 ezrin linking [46,47]. Note the extracellular β amyloid-like fragment and the nuclear and mitochondrial trafficking signals. Abbreviations for putative phosphorylation sites are: PKA, protein kinase A; PKC, protein kinase C; CKII, casein kinase II; SRC, sarcoma tyrosine kinase; INSR, insulin receptor kinase; ERM, ezrin, radixin, moesin. B: Gene structure of canonical CD44 with invariant exons 1–5, variable spliced exons 6–14, invariant exons 15–16 forming stem region, transmembrane exon 17, and cytoplasmic domain exon 19 is illustrated. Note exon 18 is spliced out [48]. Adenoviral constructs were the standard (Ad-CD44S) and truncated soluble (Ad-sCD44) isoforms; the isolated sCD44 is depicted for comparison to the constructs.