Signaling Properties of Hyaluronan Receptors*

By E. Turley, P. Noble, L. Bourguignon. Journal of Biological Chemistry, 2002

1,046 citations recorded by the source corpus.

In 1979, hyaluronan was demonstrated to bind specifically and with high affinity to intact cells (1), and in 1980, it was shown to enhance cell motility on two-dimensional culture surfaces where the hydrodynamic properties of hyaluronan were not necessary to open spaces for cells to move into (2). These two demonstrations raised the possibility that hyaluronan had the potential to directly modify cell behavior. In 1989, hyaluronan was shown to promote protein tyrosine phosphorylation cascades (3) that were later proven to be required for hyaluronan-mediated motility on planar culture surfaces (4). Since then, small amounts (nanograms) of hyaluronan have been shown to activate a variety of protein tyro- sine and serine/threonine kinases. These include the non-receptor protein tyrosine kinase Src (5, 6), HER2/Neu receptor (7), focal adhesion kinase (4, 8–10), protein kinase C (11, 12), and MAP 1 kinases (9, 10). Likely as a consequence of regulating these kinases, hyaluronan promotes expression of specific cytokines and proteins involved in extracellular matrix remodeling ( e.g. Ref. 13). The study of murine cardiac cells derived from hyaluronan synthase 2 (HAS2) knockout mice has provided the most convincing evidence for a signaling capability of hyaluronan (14). HAS2 (cid:1) / cardiac cells do not undergo an endothelial-mesenchymal transfor-

Subfields: Cell Biology, Hematology, Molecular Biology

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Citations in the corpus

Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer (2015, background): “Surprisingly, RHAMM contains no signal peptide and is thought to be transported to the cell surface via unconventional transport mechanisms, where it associates with the cell surface via docking with HA synthase (260), and like CD44, it transduces signals that influence cell motility (28, 30).”
Glycosaminoglycans and their proteoglycans: host‐associated molecular patterns for initiation and modulation of inflammation (2006, background): “Similar to CD44, RHAMM can be alternatively spliced, and has also been found both extracellularly and intracellularly (109).”
Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory (2019, background): “The effects of HA are mostly mediated by interactions with cell surface receptors (CD44, RHAMM, LYVE, and TLR2 and TLR-4) that, when activated, bind and respond to HA (308, 309).”
CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. (2006, background): “Two studies also have reported a functional, cell-surface association between CD74 and CD44 (Naujokas et al., 1993, 1995), which has known tyrosine kinase activation properties (Turley et al., 2002).”
The Structure of Glycosaminoglycans and their Interactions with Proteins (2008, background): “Many cells also express receptor for hyaluronan and motility (RHAMM), which is a major HA-binding membrane protein (20), and this RHAMM pathway induces focal adhesions and signals the cytoskeletal changes, hence elevating cell motility seen in tumour progression, invasion and metastasis.”
Hyaluronan: from extracellular glue to pericellular cue (2004, background): “CD44v(3,8-10) is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells.”
The sweet and sour of cancer: glycans as novel therapeutic targets (2005, background): “fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=960">CD44 (a transmembrane glycoprotein) as well as CD168, activate signal-transduction pathways that promote cytoskeletal changes involved in cell motility and growt”
Hyaluronic Acid in the Third Millennium (2018, background): “HA-CD44 interaction is involved in a variety of intracellular signaling pathways that control cell biological processes: receptor-mediated hyaluronan internalization/degradation, angiogenesis, cell migration, proliferation, aggregation and adhesion to ECM components [46,51,60,100,122].”
Extracellular matrix structure. (2016, background): “CD44, RHAMM, and the HA-binding PG versican [29-31] (Fig.”
Hyaluronic acid (hyaluronan): a review (2018, background): “…transport, supramolecular assembly of proteoglycans in the extracellular matrix, and numerous receptor-mediated roles in cell detachment, mitosis, migration, tumor development and metastasis, and inflammation (Balazs et al., 1986; Toole et al., 2002; Turley et al., 2002; Hascall et al., 2004).”
Targeting of CD44 eradicates human acute myeloid leukemic stem cells (2006, background): “Beyond its adhesion function, CD44 can also transduce multiple intracellular signal transduction pathways when ligated with hyaluronan or specific function-activating mAb”
The blood-brain barrier: an engineering perspective (2013, background): “Typical time averaged values of shear stress are 4–30 dynes cm−2 in the arterial circulation and 1–4 dynes cm−2 in the venous circulation (Turitto, 1982; Kamiya et al., 1984; Papaioannou and Stefanadis, 2005; Koutsiaris et al., 2007; Dolan et al., 2013).”
From Cell–ECM interactions to tissue engineering (2004, background): “It is present in all living organisms and plays an important role in many biological processes, such as matrix structure, water balance, lubrication, cell movement, and differentiation (Turley et al., 2002).”
Hyaluronan: A Simple Polysaccharide with Diverse Biological Functions (2013, background): “as c-Src, Ras and MAPKs [73], thereby regulating cell growth and survival, cytoskeletal rearrangement and active cell migration.”