MJO Wakelam's research while affiliated with University of Birmingham and other places

What is this page?


This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.

It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.

If you're a ResearchGate member, you can follow this page to keep up with this author's work.

If you are this author, and you don't want us to display this page anymore, please let us know.

Publications (11)


Polyisoprenyl phosphate signaling inhibits phospholipase D: Novel intracellular "stop" signals for neutrophils.
  • Article

January 1999

·

5 Reads

Journal of Leukocyte Biology

·

JM Clark

·

MJO Wakelam

·

Share







WORTMANNIN AND ITS STRUCTURAL ANALOG DEMETHOXYVIRIDIN INHIBIT STIMULATED PHOSPHOLIPASE A(2) ACTIVITY IN SWISS 3T3 CELLS - WORTMANNIN IS NOT A SPECIFIC INHIBITOR OF PHOSPHATIDYLINOSITOL 3-KINASE

October 1995

·

3 Reads

·

124 Citations

Journal of Biological Chemistry

Wortmannin and its structural analogue demethoxy-viridin (DMV) have been reported to be specific inhibitors of phosphatidylinositol 3-kinase activity. Here we report that these compounds are not as selective as assumed and demonstrate inhibition of bombesin stimulated phospholipase A(2) activity by both wortmannin and DMV with an IC50 (2 nM) which is slightly more potent than the inhibition of insulin-stimulated phosphatidylinositol 3,4,5-trisphosphate generation in these cells (similar to 10 nM). While it has not been possible to fully block in vitro phospholipase A(2) activity with wortmannin, inhibition cannot be a consequence of inhibition of PI 3-kinase activity since bombesin fails to generate 3-phosphorylated lipids in the intact cell. Therefore, while wortmannin is indeed a PI S-kinase inhibitor, it is not as specific as previously reported, and experimental conclusions based solely on its use should be treated with caution.




Citations (1)


... Binding required lysine (119,121) and arginine (179), and the PLD1 PX-domain also displayed modest affinity PtdIns3P as well as for PtdIns5P [139]. In addition to binding of these phosphoinositides, the PLD1 PX-domain can simultaneously bind PtdOH or PtdSer, and potentially other ionic lipids due to the presence of a second distinct lipid-binding pocket, dual occpacy of these pockets increases membrane association and likely plays a role in spatiotemporal PLD1 regulation [139].The in vivo role of PI-3-kinase in regulation of PLD activity is complicated by the fact that while PI-3-kinase inhibitors such as wortmannin inhibit cellular PLD activity, they are non-specific and affect multiple other pathways [248]. In addition, PI-3-kinase may regulate PLD through indirect mechanisms, including lipid-binding proteins such as the cytohesin [249] and Tiam-1 [250] exchange factors regulating Arf-, and Rho, whose activity is controlled by PtdIns(3,4,5)P 3 -dependent PH-domains. ...

Reference:

Mammalian phospholipase D: Function, and therapeutics
WORTMANNIN AND ITS STRUCTURAL ANALOG DEMETHOXYVIRIDIN INHIBIT STIMULATED PHOSPHOLIPASE A(2) ACTIVITY IN SWISS 3T3 CELLS - WORTMANNIN IS NOT A SPECIFIC INHIBITOR OF PHOSPHATIDYLINOSITOL 3-KINASE
  • Citing Article
  • October 1995

Journal of Biological Chemistry