Identification of NEK3 Kinase Threonine 165 as a Novel Regulatory Phosphorylation Site That Modulates Focal Adhesion Remodeling Necessary for Breast Cancer Cell Migration.

摘要: Accumulating evidence supports a role for prolactin (PRL) in the development and progression of human breast cancer. Although PRL is an established chemoattractant cancer cells, precise molecular mechanisms how regulates cell motility invasion are not fully understood. activates serine/threonine kinase NEK3, which was reported to enhance migration, invasion, actin cytoskeletal reorganization necessary these processes. However, specific NEK3 activation response signaling have been defined. In this report, novel PRL-inducible regulatory phosphorylation site within segment threonine 165 (Thr-165), identified. Phosphorylation at Thr-165 found be dependent on extracellular signal-regulated 1/2 (ERK1/2) pathway using both pharmacological inhibition siRNA-mediated knockdown approaches. Strikingly, by expression phospho-deficient mutant (NEK3-T165V) resulted increased focal adhesion size, formation zyxin-positive adhesions, cytoskeleton into stress fibers. Concordantly, NEK3-T165V cells exhibited migratory defects. Together, data support modulatory maturation and/or turnover promote migration.