Tumour necrosis factor-α (TNFα) has been reported to induce potent growth inhibition of committed myeloid progenitor cells, whereas it is a potential growth stimulator of human CD34+CD38- multipotent haematopoietic cells. The present study was aimed at evaluating the respective role of two phospholipases, phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD) in the response of the CD34+ CD38- KG1a cells to TNFα. In these cells TNFα triggered phosphoinositide 3-kinase (PI3K)-dependent PC hydrolysis within 4–8min with concomitant production of both diacylglycerol (DAG) and phosphocholine (P-chol). DAG and P-chol production was accompanied by extracellular-signal-related protein kinase-1 (‘ERK-1’) activation and DNA-synthesis stimulation. PC-PLC stimulation was followed by PI3K-independent PLD activation with concomitant phosphatidic acid (PA) production followed by PA-derived DAG accumulation and sustained nuclear factor κB (NF-κB) activation. PLD/NF-κB signalling activation played no role in the TNFα proliferative effect and conferred no consistent protection of KG1a cells towards antileukaemic agents. Altogether these results suggest that, in KG1a cells, TNFα can stimulate in parallel PC-PLC and PLD, whose lipid products activate in turn mitogen-activated protein kinase (MAP kinase) and NF-κB signalling respectively. Finally, our study suggests that PC-PLC, but not PLD, plays a role in the TNFα proliferative effect in immature myeloid cells.
Skip Nav Destination
Article navigation
October 2000
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
October 10 2000
Phosphatidylcholine-specific phospholipase C and phospholipase D are respectively implicated in mitogen-activated protein kinase and nuclear factor κB activation in tumour-necrosis-factor-α-treated immature acute-myeloid-leukaemia cells
Isabelle PLO;
Isabelle PLO
1
*INSERM E9910, Institut Claudius Regaud, Toulouse 31052, France
1To whom correspondence should be addressed (e-mail plo@icr.fnclcc.fr).
Search for other works by this author on:
Dominique LAUTIER;
Dominique LAUTIER
*INSERM E9910, Institut Claudius Regaud, Toulouse 31052, France
Search for other works by this author on:
Thierry LEVADE;
Thierry LEVADE
†INSERM U466, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse, France
Search for other works by this author on:
Hadef SEKOURI;
Hadef SEKOURI
*INSERM E9910, Institut Claudius Regaud, Toulouse 31052, France
Search for other works by this author on:
JeanPierre JAFFRÉZOU;
JeanPierre JAFFRÉZOU
*INSERM E9910, Institut Claudius Regaud, Toulouse 31052, France
Search for other works by this author on:
Guy LAURENT;
Guy LAURENT
*INSERM E9910, Institut Claudius Regaud, Toulouse 31052, France
‡Service d'Hématologie, Centre Hospitalier Universitaire Purpan, 31059 Toulouse, France
Search for other works by this author on:
Ali BETTAÏEB
Ali BETTAÏEB
§INSERM U517, Mort cellulaire et cancer, UFR de Pharmacie, 21033 Dijon, France
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 17 2000
Revision Received:
July 13 2000
Accepted:
August 09 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 351 (2): 459–467.
Article history
Received:
March 17 2000
Revision Received:
July 13 2000
Accepted:
August 09 2000
Citation
Isabelle PLO, Dominique LAUTIER, Thierry LEVADE, Hadef SEKOURI, JeanPierre JAFFRÉZOU, Guy LAURENT, Ali BETTAÏEB; Phosphatidylcholine-specific phospholipase C and phospholipase D are respectively implicated in mitogen-activated protein kinase and nuclear factor κB activation in tumour-necrosis-factor-α-treated immature acute-myeloid-leukaemia cells. Biochem J 15 October 2000; 351 (2): 459–467. doi: https://doi.org/10.1042/bj3510459
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.