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Review
. 2009 May;21(5):651-5.
doi: 10.1016/j.cellsig.2009.01.024. Epub 2009 Jan 13.

Rheostatic signaling by CD44 and hyaluronan

Ellen Puré  1 , Richard K Assoian
Affiliations
Review

Rheostatic signaling by CD44 and hyaluronan

Ellen Puré et al. Cell Signal. 2009 May.

Abstract

Cellular function and adaptive behavior is often driven by signals generated in response to the local tissue microenvironment. Cell surface receptors that detect changes in extracellular matrix composition and modifications to extracellular matrix components, are ideally positioned to provide highly responsive sensors of changes in the microenvironment and mediate changes in cellular function required to maintain tissue integrity. Receptors can act as "on/off" switches, but ligand/receptor complexes that provide "rheostatic" control may be more sensitive, provide a more rapid mechanism of control and allow for fine-tuning of cellular responses to the microenvironment. Herein, we review evidence that transitions in the physiochemical properties of the extracellular glycosaminoglycan hyaluronan and in the function of its major receptor, CD44, differentially regulate ERK and Rac signal transduction pathways to provide critical rheostatic control of mesenchymal cell proliferation.

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Figures

Figure 1
Figure 1
Working model showing how inflammation-associated changes in the molecular weight of HA may regulate the phosphorylation of merlin, the association of ERM proteins, and the ERK and Rac signaling pathways to cyclin D1, leading to rheostatic control of cell proliferation.
Figure 2
Figure 2
Working model of the interplay between inflammation, HA, CD44 and mitogenic signaling in response to tissue damage or injury.
See this image and copyright information in PMC

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