Short, Sarah M.Derrien, AlexandrineNarsimhan, Radha P.Lawler, JackIngber, Donald E.Zetter, Bruce R.2019-10-032005Short, Sarah M., Alexandrine Derrien, Radha P. Narsimhan, Jack Lawler, Donald E. Ingber, and Bruce R. Zetter. 2005. “Inhibition of Endothelial Cell Migration by Thrombospondin-1 Type-1 Repeats Is Mediated by β1integrins.” The Journal of Cell Biology 168 (4): 643–53. https://doi.org/10.1083/jcb.200407060.0021-95251540-8140http://nrs.harvard.edu/urn-3:HUL.InstRepos:41467425The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane receptor. We now report that the TSR domain can inhibit VEGF-induced migration in human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover, we identified beta(1) integrins as a critical receptor in TSR-mediated inhibition of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential for TSR-mediated inhibition of HUVEC migration, but that neither PLCgamma nor Akt was necessary for this response. Furthermore, beta1 integrins were critical for TSR-mediated inhibition of microvascular endothelial cells, cells that express CD36. Together, our results indicate that P, integrins mediate the anti-migratory effects of TSR through a PI3k-dependent mechanism.en-USJournal Article2019-10-0310.1083/jcb.200407060