Pim-3 is expressed in endothelial cells and promotes vascular tube formation.
Pim-3 is a member of proto-oncogene Pim family that encodes serine/threonine kinases. Pim proteins regulate both apoptosis and cellular metabolism by phosphorylating their substrates. Here, we report for the first time that Pim-3 is highly expressed at mRNA and protein levels in endothelial cells (ECs). We found that Pim-3 is concentrated at the cellular lamellipodia and co-localized with focal adhesion kinase (FAK). Pim-3 was dispersed from lamellipodia when ECs were treated with cytochalasin D, an inhibitor of actin polymerization. In addition, small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired EC spreading, migration, and proliferation, leading to a reduction in tube-like structure formation in a Matrigel assay. These results provide the novel evidence that Pim-3 plays an essential role in EC spreading and migration, suggesting that Pim-3 may be an important molecular target for the development of small-molecule inhibitors of angiogenesis.
Zhang
Peng
P
Institute of Cardiovascular Science, DongFeng Hospital, YunYang Medical College, Hubei, China. zhangnep@yahoo.cn
Wang
Hanqin
H
Min
Xinwen
X
Wang
Yinfang
Y
Tang
Jie
J
Cheng
Jishun
J
Li
Dongfeng
D
Chen
Xin
X
Cheng
Fanjun
F
Wang
Nanping
N
Yang
Handong
H
D008841:Actin Cytoskeleton / Q000201:enzymology; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000201:enzymology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D022502:Stress Fibers / Q000201:enzymology; D013997:Time Factors
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015638:Cytochalasin D; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C499249:PIM3 protein, human; C113398:Pim3 protein, rat; D017346:Protein Serine-Threonine Kinases