PKCδ‐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 of cell growth and differentiation, apoptosis, and inflammation. The mitogen phorbol 12‐myristate 13‐acetate (PMA) induces expression and phosphorylation of ANX‐1. However, the roles of ANX‐1 in PMA‐induced signal transduction is unknown. Here, we study the cellular localization of ANX‐1 in the PMA‐induced signal transduction process. We have found that PMA induces the cleavage of ANX‐1 in human embryonic kidney (HEK) 293 cells, and that the cleaved form of ANX‐1 translocates to the nucleus. The PMA‐induced nuclear translocation of ANX‐1 was inhibited by the protein kinase C (PKC)δ‐specific inhibitor rottlerin, indicating that PKCδ plays a role in nuclear translocation of the cleaved ANX‐1. We propose a novel mechanism of PMA‐induced translocation of ANX‐1 to the nucleus that may participate in the regulation of cell proliferation and differentiation.