Premium
Tributyltin causes activation of the MAP3K, c‐Raf, but not Ras in human natural killer cells
Author(s) -
Celada Lindsay,
Whalen Margaret
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.862.2
Subject(s) - tributyltin , mapk/erk pathway , kinase , microbiology and biotechnology , protein kinase a , phosphorylation , chemistry , map kinase kinase kinase , lytic cycle , biology , immunology , virus , organic chemistry
The toxic chemical tributyltin (TBT) has been found in human blood. TBT is employed in various industrial applications and due to these uses contaminates the environment. Human natural killer (NK) cells are a subset of lymphocytes capable of destroying tumor cells, virally infected cells, and antibody‐coated cells. It has been shown that TBT is able to diminish the lytic function of NK cells. Previous studies have demonstrated that exposure to TBT leads to the activation of Mitogen‐Activated‐Protein‐Kinase (MAPK) and MAPK‐Kinase (MAP2K) in NK cells. TBT also results in the activation of the MAPK Kinase‐Kinase (MAP3K), c‐Raf, at an exposure time of ten minutes in NK cells. Activation/phosphorylation of c‐Raf (Ser338) was seen with exposure to 300, 200, 100, and 50 nM TBT (2 fold at 300–100 nM and 1.45 fold at 50 nM). Increased phosphorylation of Ser259 was also seen with 300–200 nM TBT (2 and 1.7 fold, respectively). Ras is a GTPase which is known to lead to the activation of the MAP3Ks. In its inactive state, Ras is bound to GDP; but when activated, it binds GTP. The focus of this study was to see if there was a TBT‐induced activation of Ras that leads to activation of Raf in NK cells. It was found that exposure to TBT in these cells did not result in the activation of Ras; indicating that there is an alternative mechanism for activation of Raf by TBT. Supported by NIH grant S06 GM008092‐34