1. ^*Department of Dermatology, University of Rochester, Rochester, New York, and Johnson and Johnson Skin Research Center, Skillman, New Jersey, USA
2. ^†Department of Pathology, University of Rochester, Rochester, New York, and Johnson and Johnson Skin Research Center, Skillman, New Jersey, USA

Correspondence: Glynis Scott, Box 697, Department of Dermatology, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14618, Email: Glynis_Scott@urmc.rochester.edu

Received 17 February 2003; Revised 26 March 2003; Accepted 7 April 2003; Published online 18 August 2003.

Abstract

Recent work shows that the G-protein-coupled receptor proteinase activated receptor-2 activates signals that stimulate melanosome uptake in keratinocytes in vivo and in vitro. The Rho family of GTP-binding proteins is involved in cytoskeletal remodeling during phagocytosis. We show that proteinase-activated receptor-2 mediated phagocytosis in human keratinocytes is Rho dependent and that proteinase-activated receptor-2 signals to activate Rho. In contrast, Rho activity did not affect either proteinase-activated receptor-2 activity or mRNA and protein levels. We explored the signaling mechanisms of proteinase-activated receptor-2 mediated Rho activation in human keratinocytes and show that activation of proteinase-activated receptor-2, either through specific proteinase-activated receptor-2 activating peptides or through trypsinization, elevates cAMP in keratinocytes. Proteinase-activated receptor-2 mediated Rho activation was pertussis toxin insensitive and independent of the protein kinase A signaling pathway. These data are the first to show that proteinase-activated receptor-2 mediated phagocytosis is Rho dependent and that proteinase-activated receptor-2 signals to Rho and cAMP in keratinocytes. Because phagocytosis of melanosomes is recognized as an important mechanism for melanosome transfer to keratinocytes, these results suggest that Rho is a critical signaling intermediate in melanosome uptake in keratinocytes.