Extracellular phosphorylation of C9 by protein kinase CK2 regulates complement-mediated lysis.
Ecto-protein kinases (ecto-PK) are expressed on many cell types, both normal and malignant, yet their functions are largely unknown. An ecto-PK capable of phosphorylating the C9 component of the complement system is described. This C9 ecto-PK could be inhibited by TBB, Emodin and DRB, selective inhibitors of protein kinase CK2. Treatment of Raji human B lymphoma cells with these CK2 inhibitors augmented cell killing by Rituximab (anti-CD20 antibodies) and human complement. Analysis of C5b-7-bearing Raji cells showed that extracellular inhibition of the ecto-CK2 enhanced cell lysis by C8 and C9. Blocking of the membrane complement regulator CD59 with monoclonal antibodies further enhanced the effect of the CK2 inhibitors on Raji cell death by complement. C9 ecto-CK2 activity was increased on cancer cells relative to normal fibroblasts and blood cells. Therefore, ecto-CK2 appears to be an additional factor protecting cells from complement-mediated lysis, probably by phosphorylation/inhibition of complement C9.
Bohana-Kashtan
Osnat
O
Department of Cell and Developmental Biology, Sackler School of Medicine,Tel Aviv University, Tel Aviv, Israel.
Pinna
Lorenzo A
LA
Fishelson
Zvi
Z
D047390:Casein Kinase II / Q000502:physiology*; D003186:Complement C9 / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D020014:K562 Cells; D010766:Phosphorylation; D011480:Protease Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology*
D003186:Complement C9; D011480:Protease Inhibitors; D011494:Protein Kinases; C034454:ectoprotein kinase; D047390:Casein Kinase II