title: Interplay between integrins and FLK-1 in shear stress-induced signaling.
abstract: Blood flow can modulate vascular cell functions. We studied interactions between integrins and Flk-1 in transducing the mechanical shear stress due to flow. This application of a step shear stress caused Flk-1. Casitas B-lineage lymphoma (Cbl) activation (Flk-1. Cbl association, tyrosine phosphorylation of the Cbl-bound Flk-1, and tyrosine phosphorylation of Cbl) in bovine aortic endothelial cells (BAECs). The activation of integrins by plating BAECs on vitronectin or fibronectin also induced this Flk-1. Cbl activation. The shear-induced Flk-1. Cbl activation was blocked by inhibitory antibodies for alphavbeta3- or beta1-integrin, suggesting that it is mediated by integrins. Inhibition of Flk-1 by SU1498 also abolished this shear-induced Flk-1. Cbl activation. In contrast to the requirement of integrins for Flk-1. Cbl activation, the Flk-1 blocker SU1498 had no detectable effect on the shear-induced integrin activation, suggesting that integrins and Flk-1 play sequential roles in the signal transduction hierarchy induced by shear stress. Integrins are essential for the mechanical activation of Flk-1 by shear stress but not for the chemical activation of Flk-1 by VEGF.
authors.affiliation: Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Miao
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Kuang-Den
authors.initials: KD
authors.lastname: Chen
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Li
authors.forename: Suli
authors.initials: S
authors.lastname: Yuan
authors.forename: John Y-J
authors.initials: JY
authors.lastname: Shyy
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008024:Ligands; D008222:Lymphokines / Q000494:pharmacology; D016393:Lymphoma, B-Cell; D050722:Oncogene Protein v-cbl; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016228:Endothelial Growth Factors; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008222:Lymphokines; D050722:Oncogene Protein v-cbl; D011506:Proteins; D019030:Receptors, Vitronectin; D015682:Retroviridae Proteins, Oncogenic; D055765:Shc Signaling Adaptor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014443:Tyrosine; D040301:Vascular Endothelial Growth Factor Receptor-2