tailieunhanh - Báo cáo khoa học: PKCd-dependent cleavage and nuclear translocation of annexin A1 by phorbol 12-myristate 13-acetate

Annexin A1 (ANX-1), a calcium-dependent, phospholipid binding protein, is known to be involved in diverse cellular processes, including regulation ofcell growth and differen-tiation, apoptosis, and inflammation. The mitogen phorbol 12-myristate 13-acetate (PMA) induces expression and phosphorylation ofANX-1. However, the roles of ANX-1 in PMA-induced signal transduction is unknown. Here, we study the cellular localization ofANX-1 in the PMA-induced signal transduction process. | Eur. J. Biochem. 270 4089-4094 2003 FEBS 2003 doi PKCd-dependent cleavage and nuclear translocation of annexin A1 by phorbol 12-myristate 13-acetate Xf AM c I im1 I a2 Im c l ii 1 Ciimm IAIiiL I mm2 Ua I ChmmZ I I 1 cs f I 1 If a 3 Yoon S. Kim Jesang Ko In S. Kim Sung-Wuk Jang Ho J. Sung Hye J. Lee SI Y. Lee Youngho Kim and Doe S. Na1 1 Department of Biochemistry and Molecular Biology 2Asan Institute for Life Sciences and 3Genome Research Center for Birth Defects and Genetic Diseases University of Ulsan College of Medicine Seoul Korea Annexin A1 ANX-1 a calcium-dependent phospholipid binding protein is known to be involved in diverse cellular processes including regulation of Clll growth and difleren-tiation apoptosis and inflammation. The mitogen phorbol 12-myristate 13-acetate PMA induces expression and phosphorylation of A2XG1. However the oofes oANXX-1 in PMA-induced signal transduction is unknown. Here we study the cellular localization of A NX-1 in the PMA-induced signal transduction process. We have found that PMA induces the cleavage ofANX-1 in human embryonic kidney HEK 293 cells and that the cleaved form of ANX-1 translocates to the nucleus. The PMA-i induced nuclear translocation of ANX4 was mhibited by the protein kinase C PKC S-specific inhibitor rottlerin indicating that PKCỖ plays a role in nuclear translocation of the cleaved ANX-1. We propose a novel mechanism of PMA-induced translocation ofANX-1 to the nucleus that may participate in the regulation ofcell proliefration and differentiation. Keywords annexin A1 PMA cleavage nuclear translocation PKCỖ. Annexins ANXs are a family of calcium-dependent phospholipid-binding proteins. Several members of tìie ANX family are known to be involved in various physiological functions including anti-inflammatory processes cell signaling regulation ofcell growth and defirfentiation apoptosis membrane fusion exocytosis and interaction with cytoskeletal proteins 1-3 . .