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Thrombospondins and Their Receptors: Evolving Functions

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Evolution of Extracellular Matrix

Part of the book series: Biology of Extracellular Matrix ((BEM))

Abstract

Since the discovery of thrombospondin-1 (TSP1) in the 1970s, and the gradual unveiling of four more members of the mammalian TSP family, the field has been in pursuit of two fundamental questions: what are the physiological roles of these large multidomain glycoproteins and which receptors and signaling pathways mediate these functions? This has been a complex task because TSPs interact with multiple receptors and extracellular binding partners via their several domains. The multidomain structure of the TSP subunits, their trimeric or pentameric quaternary structure, and the promiscuity of their receptors combine to present us with a veritable “Rubic’s Cube” of possible functions and mechanisms of action. In this chapter we provide a current overview of progress in solving this puzzle. We present a brief overview of the structure and evolution of the TSP family members and the receptors that recognize various domains of TSPs. These advances have led to the identification of important pathophysiological roles for certain TSP family members and revealed opportunities to develop novel therapeutics.

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Acknowledgments

This work was supported by the Intramural Research Program of the NIH/NCI (D.D.R.) and by grants from the NIH (W.A.F.).

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Correspondence to William A. Frazier .

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Roberts, D.D., Frazier, W.A. (2013). Thrombospondins and Their Receptors: Evolving Functions. In: Keeley, F., Mecham, R. (eds) Evolution of Extracellular Matrix. Biology of Extracellular Matrix. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36002-2_8

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