Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) affects RhoA activation in endothelial cells.
Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) expressed in endothelial cells (ECs) plays an important role in angiogenesis due to its involvement in migration, proliferation and network formation. Here we examined the biological function of PILSAP with respect to EC morphogenesis and the related intracellular signaling for this process. When mouse endothelial MSS31 cells were cultured, a dominant negative PILSAP mutant converted cell shape to disk-like morphology, blocked stress fiber formation, and augmented membrane ruffling in random directions. These phenotypic changes led us to test whether PILSAP affected activities of Rho family small G-proteins. Abrogation of PILSAP enzymatic activity or its expression attenuated RhoA but not Rac1 activation during cell adhesion. This attenuation of RhoA activation was also evident when G-protein coupled receptors such as proteinase-activated receptor or lysophosphatidic acid receptor were activated in ECs. These results indicate that PILSAP affects RhoA activation and that influences the proper function of ECs.
Suzuki
Takahiro
T
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Abe
Mayumi
M
Miyashita
Hiroki
H
Kobayashi
Toshimitsu
T
Sato
Yasufumi
Y
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology*; D007931:Leucyl Aminopeptidase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein