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J. Biol. Chem., Vol. 283, Issue 31, 21305-21309, August 1, 2008

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Minireview

Biological Functions of the Small Leucine-rich Proteoglycans: From Genetics to Signal Transduction^*

Liliana Schaefer and Renato V. Iozzo¹

From the Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany and the Department of Pathology, Anatomy, and Cell Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

The small leucine-rich proteoglycan (SLRP) family has significantly expanded in the past decade to now encompass five discrete classes, grouped by common structural and functional properties. Some of these gene products are not classical proteoglycans, whereas others have new and unique features. In addition to being structural proteins, SLRPs constitute a network of signal regulation: being mostly extracellular, they are upstream of multiple signaling cascades. They affect intracellular phosphorylation, a major conduit of information for cellular responses, and modulate distinct pathways, including those driven by bone morphogenetic protein/transforming growth factor β superfamily members, receptor tyrosine kinases such as ErbB family members and the insulin-like growth factor I receptor, and Toll-like receptors. The wealth of mechanistic insights into the molecular and cellular functions of SLRPs has revealed both the sophistication of this family of regulatory proteins and the challenges that remain in uncovering the totality of their functions. This review is focused on novel biological functions of SLRPs with special emphasis on their protein cores, newly described genetic diseases, and signaling events in which SLRPs play key functions.

^* This work was supported, in whole or in part, by National Institutes of Health Grants RO1 CA39481, RO1 CA47282, and RO1 CA120975 (to R. V. I.). This work was also supported by Deutsche Forschungsgemeinschaft Grant SFB 492 (to L. S.). This minireview will be reprinted in the 2008 Minireview Compendium, which will be available in January, 2009.

¹ To whom correspondence should be addressed. E-mail: iozzo{at}mail.jci.tju.edu.

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