title: Coronin 1B serine 2 phosphorylation by p38α is critical for vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
abstract: Coronin 1B is an actin-binding protein that regulates various cellular processes including cell motility. However, the role of coronin 1B in vascular cell migration remains controversial. Here, we examined the function of coronin 1B in vascular endothelial growth factor (VEGF)-induced migration of human umbilical vein endothelial cells (HUVECs) and investigated the mechanism by which coronin 1B regulates this cellular process. We found that depletion of coronin 1B increased the VEGF-induced migration of HUVECs. VEGF phosphorylated coronin 1B at Ser2 and stimulated its translocation to the leading edge of stimulated cells. Lentivirus-mediated overexpression of wild-type coronin 1B or a phosphodeficient coronin 1B S2A mutant decreased VEGF-induced transwell migration of HUVECs. Treatment with the p38 inhibitor SB203580 or depletion of p38α by small interfering RNA transfection decreased VEGF-induced coronin 1B phosphorylation. In vitro binding and kinase assays revealed that active p38α directly binds to and phosphorylates coronin 1B at Ser2. In addition, VEGF induced active p38α binding to coronin 1B in HUVECs. VEGF disrupted the interaction between coronin 1B and the actin-related protein (Arp)2/3 complex and p38α depletion prevented this VEGF-induced dissociation. These findings suggest that coronin 1B plays an inhibitory role in VEGF-induced migration of HUVECs and that VEGF-activated p38α phosphorylates coronin 1B at Ser2 and activates the Arp2/3 complex by liberating it from coronin 1B.
authors: Division of Cardiovascular and Rare Disease, Center for Biomedical Sciences, Korea National Research Institute of Health, Cheongju, Republic of Korea; Juju National Quarantine Station, Centers for Disease Control & Prevention, Jeju, Republic of Korea.
authors: Geun-Young
authors: GY
authors: Kim
authors: Division of Cardiovascular and Rare Disease, Center for Biomedical Sciences, Korea National Research Institute of Health, Cheongju, Republic of Korea.
authors: Jin-Hee
authors: JH
authors: Park
authors: Division of Cardiovascular and Rare Disease, Center for Biomedical Sciences, Korea National Research Institute of Health, Cheongju, Republic of Korea.
authors: Hanna
authors: H
authors: Kim
authors: Division of Cardiovascular and Rare Disease, Center for Biomedical Sciences, Korea National Research Institute of Health, Cheongju, Republic of Korea.
authors: Hyun-Joung
authors: HJ
authors: Lim
authors: Division of Cardiovascular and Rare Disease, Center for Biomedical Sciences, Korea National Research Institute of Health, Cheongju, Republic of Korea. Electronic address: mdhypark@gmail.com.
authors: Hyun-Young
authors: HY
authors: Park
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C072061:coronin proteins; D010768:Phosphoserine; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Coronin 1B; Human umbilical vein endothelial cells; Migration; Vascular endothelial growth factor; p38α