reduced prostasin (cap1prss8) activity eliminates hai-1 and hai-2 deficiency–associated developmental defects by preventing matriptase activation减少prostasin(cap1prss8)活动消除hai-1 hai-2缺乏引起发育缺陷通过防止matriptase激活.pdfVIP

Reduced Prostasin (CAP1/PRSS8) Activity Eliminates HAI- 1 and HAI-2 Deficiency–Associated Developmental Defects by Preventing Matriptase Activation 1 1 1 1 1,2,3 Roman Szabo , Katiuchia Uzzun Sales , Peter Kosa , Natalia A. Shylo , Sine Godiksen , 1 1 1 2 4 5,6 Karina K. Hansen , Stine Friis , J. Silvio Gutkind , Lotte K. Vogel , Edith Hummler , Eric Camerer , Thomas H. Bugge1* 1 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark, 3 Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark, 4 Pharmacology and Toxicology Department, University de Lausanne, Lausanne, Switzerland, 5 INSERM U970, ´ Paris Cardiovascular Research Centre, Paris, France, 6 Universite Paris-Descartes, Paris, France Abstract Loss of either hepatocyte growth factor activator inhibitor (HAI)-1 or -2 is associated with embryonic lethality in mice, which can be rescued by the simultaneous inactivation of the membrane-anchored serine protease, matriptase, thereby demonstrating that a matriptase-dependent proteolytic pathway is a critical developmental target for both protease inhibitors. Here, we performed a genetic epistasis analysis to identify additional components of this p