期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 390, 期 4, 页码 1395-1401出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.11.004
关键词
Ras; Ras guanyl releasing protein; Diacylglycerol; Phosphatidylinositol 3-kinase; Akt/PKB; Leukocyte-derived cell lines; Epstein-Barr virus; Protein kinase C
资金
- The Canadian Institutes of Health Research
In leukocytes, diacylglycerol (DAG) regulates the small GTPase Ras through the agency of Ras guanyl releasing proteins (RasGRPs). Ras is thought to regulate phosphatidylinositol 3-kinase (PI3K). Therefore, DAG signaling is hypothesized to impact PI3K activity. The DAG analogue pico was used to activate RasGRPs in leukocyte-derived cell lines. PI3K signaling was monitored using antibodies that recognize the activated form of the PI3K-regulated protein kinase Akt. Diverse responses were documented. Some cell lines exhibit a DAG analogue-stimulated increase in phospho-Akt but this response proceeded even when Ras activation was blocked. In some Epstein-Barr virus-associated malignant cell lines and transformed B h basal phospho-Akt was decreased by DAG analogue treatment. The pan-PKC inhibitor Bisind-cells olymaleimide I blocked this effect. Basal phospho-Akt was also decreased by treatment with Go6976, an inhibitor of conventional protein kinase C and protein kinase D. While the proposed RasGRP-Ras-PI3K-Akt signaling axis may operate in some situations, our results indicate that alternative links between DAG targets such as protein kinases and the PI3K signaling system are more prominent. (C) 2009 Elsevier Inc. All rights reserved.
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