PT - JOURNAL ARTICLE AU - Katarzyna Bialkowska AU - Khalid Sossey-Alaoui AU - Elzbieta Pluskota AU - Lahoucine Izem AU - Jun Qin AU - Edward F Plow TI - Site-specific phosphorylation regulates the functions of kindlin-3 in a variety of cells AID - 10.26508/lsa.201900594 DP - 2020 Mar 01 TA - Life Science Alliance PG - e201900594 VI - 3 IP - 3 4099 - https://www.life-science-alliance.org/content/3/3/e201900594.short 4100 - https://www.life-science-alliance.org/content/3/3/e201900594.full SO - Life Sci. Alliance2020 Mar 01; 3 AB - Studies of isolated cells, mice, and humans have demonstrated the vital role of the FERM domain protein kindlin-3 in integrin activation in certain hematopoietic and non-hematopoietic cells, consequent to binding to integrin β-subunits. To explore regulatory mechanisms, we developed a monoclonal antibody that selectively recognizes the phosphorylated form of Ser484 (pS484) in kindlin-3. Activation of platelets, HEL megakaryocytic-like cells and BT549 breast cancer cells led to enhanced expression of pS484 as assessed by immunofluorescence or Western blotting. In platelets, pS484 rose rapidly and transiently upon stimulation. When a mutant form of kindlin-3, T482S484/AA kindlin-3, was transduced into mouse megakaryocytes, it failed to support activation of integrin αIIbβ3, whereas wild-type kindlin-3 did. In MDA-MB231 breast cancer cells, expression of T482S484/AA kindlin-3 suppressed cell spreading, migration, invasion, and VEGF production. Wild-type kindlin-3 expressing cells markedly increased tumor growth in vivo, whereas T482S484/AA kindlin-3 significantly blunted tumor progression. Thus, our data establish that a unique phosphorylation event in kindlin-3 regulates its cellular functions.