Tyrosine phosphatase epsilonM stimulates migration and survival of porcine aortic endothelial cells by activating c-Src.
The cell growth, survival, and migration of vascular endothelial cells (ECs) are positively regulated by several protein tyrosine kinase receptors. Therefore, protein tyrosine phosphatases (PTPs) must also be important for these processes. The present study found that transmembranal PTPepsilonM, but not cytoplasmic PTPepsilonC, is expressed in porcine ECs and in rat smooth muscle cells, both of which were prepared from the aorta. The overexpression of wild-type PTPepsilonM promoted cell survival and migration in porcine aortic ECs even in medium without and with 1% serum, respectively. A catalytically inactive, substrate-trapping mutant of PTPepsilonM, respectively, did not affect and conversely suppressed cell survival and migration. Interestingly, the forced expression of wild-type PTPepsilonC reduced cell viability in contrast to PTPepsilonM in ECs lacking endogenous PTPepsilonC, indicating the biological significance of selective expression of PTPepsilon isoforms in the vasculature. PTPepsilonM activated c-Src kinase probably by directly dephosphorylating phospho-Tyr527, a negative regulatory site of c-Src. The increases in cell survival and migration induced by overexpressed PTPepsilonM were suppressed by the c-Src inhibitor SU6656. Considering the behaviors of vascular ECs in the pathogenesis of atherosclerosis, these data suggest that PTPepsilonM negatively regulates the development of this disease by activating c-Src.
Nakagawa
Yoshimi
Y
Gene Research Center, University of Tsukuba, Ibaraki 305-8572, Japan.
Yamada
Noriaki
N
Shimizu
Hidehisa
H
Shiota
Masayuki
M
Tamura
Mariko
M
Kim-Mitsuyama
Shokei
S
Miyazaki
Hitoshi
H
D000818:Animals; D001011:Aorta / Q000166:cytology*; D001161:Arteriosclerosis / Q000201:enzymology; D000081247:CSK Tyrosine-Protein Kinase; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D007211:Indoles / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000378:metabolism; D013552:Swine; D019061:src-Family Kinases
D007211:Indoles; D007527:Isoenzymes; C416927:SU 6656; D013449:Sulfonamides; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases