STKE: Out, In, and Out Again

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Science  14 Sep 2001:
Vol. 293, Issue 5537, pp. 1957c
DOI: 10.1126/science.293.5537.1957c

Monocytes participate in inflammatory responses, wound repair, and other processes and interact with activated platelets and endothelial cells through P-selectin glycoprotein-1 (PSGL-1).

Mahoney et al. show that binding of PSGL-1 to P-selectin increases the activity of the kinase mTOR (mammalian target of rapamycin) involved in cell proliferation. Urokinase plasminogen activator receptor (UPAR) translation is enhanced to influence adhesion and migration. UPAR is also transcriptionally regulated and has multiple actions, such as interaction with extracellular matrix vitronectin. Indeed, the increased synthesis of UPAR in response to the PSGL-1 causes enhanced adhesion of monocytes to vitronectin. Thus an “outside-in” signal from interaction of a cell with P-selectin triggers an intracellular signaling pathway that ultimately signals back to the outside through increased expression of UPAR, enhancing binding to vitronectin. These changes could mediate some of the therapeutic effects of rapamycin. — LBR

Proc. Natl. Acad. Sci. U.S.A. 98, 10284 (2001).

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