CD44

What is CD44?

CD44 antigen is a cell-surface glycoprotein in humans that is encoded by CD44 gene. CD44 is expressed in a large number of mammalian cell types. The standard isoform, designated CD44s, comprising exons 1–5 and 16–20 is expressed in most cell types. CD44 splice variants containing variable exons are designated CD44v. Some epithelial cells also express a larger isoform (CD44E), which includes exons v8–10.

What is the feature of CD44 structure?

CD44 is a transmembrane molecule composed of four functional domains, including N-terminal domain, stem region, transmembrane domain and cytoplasmatic domain. The N-terminal extracellular domain mainly binds various ligands, involving hyaluronic acid (HA), extracellular matrix (ECM) glycoproteins and proteoglycans, growth factors, cytokines and matrix metalloproteinases.

In result of the proteolytic cleavage within the stem region, the extracellular domain is released into the extracellular space. The transmembrane domain anchors and stabilises the molecule in the plasma membrane. The cytoplasmic domain is responsible for signal transduction through binding to different molecules, including cytoskeleton components, kinases and activators of small Rho GTPases (GEFs-guanine nucleotide exchange factors).

What is The Function of CD44?

CD44 mainly functions as a receptor for HA. It mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Adhesion with HA plays an important role in cell migration, tumor growth and progression.

In cancer cells, CD44 may plays an important role in invadopodia formation. Moreover, it is also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events.

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