Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals.
Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1.
Diaz-Meco
M T
MT
Hospital General Gregorio Marañón, Madrid, Spain.
Dominguez
I
I
Sanz
L
L
Municio
M M
MM
Berra
E
E
Cornet
M E
ME
Garcia de Herreros
A
A
Johansen
T
T
Moscat
J
J
D000818:Animals; D001409:Bacillus cereus / Q000201:enzymology; D002460:Cell Line; D004789:Enzyme Activation; D016259:Genes, myc; D006868:Hydrolysis; D007328:Insulin / Q000502:physiology; D015603:Keratinocytes / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D008845:Microinjections; D009865:Oocytes / Q000201:enzymology; D010713:Phosphatidylcholines / Q000378:metabolism*; D011374:Progesterone / Q000502:physiology; D006656:Protamine Kinase / Q000037:antagonists & inhibitors; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis
D007328:Insulin; D010713:Phosphatidylcholines; D016212:Transforming Growth Factor beta; D011374:Progesterone; D006656:Protamine Kinase; D010738:Type C Phospholipases; D016283:Proto-Oncogene Proteins p21(ras)