PKCδ-dependent cleavage and nuclear translocation of annexin A1 by phorbol 12-myristate 13-acetate

Authors


D. S. Na, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, 388–1 Poongnap-dong, Songpa-gu, Seoul 138–736, Korea. Fax: + 82 2 477 9715, Tel.: + 82 2 3010 4275, E-mail: dsna@amc.seoul.kr

Abstract

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.

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