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Veterinary Medicine

University of Massachusetts Amherst

Ana Maria Salicioni

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Regulation Of Rac1 Activation By The Low Density Lipoprotein Receptor–Related Protein, Zhong Ma, Keena S. Thomas, Donna J. Webb, Radim Moravec, Ana Maria Salicioni, Wendy M. Mars, Steven L. Gonias Dec 2002

Regulation Of Rac1 Activation By The Low Density Lipoprotein Receptor–Related Protein, Zhong Ma, Keena S. Thomas, Donna J. Webb, Radim Moravec, Ana Maria Salicioni, Wendy M. Mars, Steven L. Gonias

Ana Maria Salicioni

The low density lipoprotein receptor–related protein (LRP-1) binds and mediates the endocytosis of multiple ligands, transports the urokinase-type plasminogen activator receptor (uPAR) and other membrane proteins into endosomes, and binds intracellular adaptor proteins involved in cell signaling. In this paper, we show that in murine embryonic fibroblasts (MEFs) and L929 cells, LRP-1 functions as a major regulator of Rac1 activation, and that this activity depends on uPAR. LRP-1–deficient MEFs demonstrated increased Rac1 activation compared with LRP-1–expressing MEFs, and this property was reversed by expressing the VLDL receptor, a member of the same gene family as LRP-1, with overlapping ligand-binding specificity. …