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2016 ; 10
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): 121-7
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Cell surface receptors for CCN proteins
#MMPMID27098435
Lau LF
J Cell Commun Signal
2016[Jun]; 10
(2
): 121-7
PMID27098435
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The CCN family (CYR61; CTGF; NOV; CCN1-6; WISP1-3) of matricellular proteins in
mammals is comprised of six homologous members that play important roles in
development, inflammation, tissue repair, and a broad range of pathological
processes including fibrosis and cancer. Despite considerable effort to search
for a high affinity CCN-specific receptor akin to growth factor receptors, no
such receptor has been found. Rather, CCNs bind several groups of multi-ligand
receptors as characteristic of other matricellular proteins. The most extensively
documented among CCN-binding receptors are integrins, including ?v?3, ?v?5, ?5?1,
?6?1, ?IIb?3, ?M?2, and ?D?2, which mediate diverse CCN functions in various cell
types. CCNs also bind cell surface heparan sulfate proteoglycans (HSPGs), low
density liproprotein receptor-related proteins (LRPs), and the cation-independent
mannose-6-phosphate (M6P) receptor, which are endocytic receptors that may also
serve as co-receptors in cooperation with other cell surface receptors. CCNs have
also been reported to bind FGFR-2, Notch, RANK, and TrkA, potentially altering
the affinities of these receptors for their ligands. The ability of CCNs to bind
a multitude of receptors in various cell types may account for the remarkable
versatility of their functions, and underscore the diverse signaling pathways
that mediate their activities.
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