Kinetic evidence of a rapid activation of phosphatidylcholine hydrolysis by Ki-ras oncogene. Possible involvement in late steps of the mitogenic cascade.
A novel phospholipase C specific for phosphatidylcholine has been shown to be activated by several agonists. Also, recent evidence suggests that transformation mediated by the ras oncogene possibly involves the activation of this novel phospholipid degradative pathway which would account for the increased diacylglycerol levels associated with transformation. Here we use a mutant of Ki-ras which is temperature-sensitive for transformation to investigate the kinetics of activation of the phosphodiesterase-mediated turnover of phosphatidylcholine. Upon shift to the permissive temperature, products of the activated phosphatidylcholine-specific phospholipase C were detected by 30 min and reached maximal levels by 1-2 h. These results suggest that the product of the ras oncogene rapidly activates the phosphodiesteratic hydrolysis of phosphatidylcholine. Furthermore, the fact that at least 4 h are required for serum to activate this phospholipase C strongly suggests that the ras oncogene product might be involved in late steps of the mitogenic signaling cascade.
Medicina y Cirugia Experimental, Hospital General Gregorio Marañon, Madrid, Spain.
M
M
Lopez-Barahona
P L
PL
Kaplan
M E
ME
Cornet
M T
MT
Diaz-Meco
P
P
Larrodera
I
I
Diaz-Laviada
A M
AM
Municio
J
J
Moscat
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D011905:Genes, ras; D020404:Glycerophospholipids; D006868:Hydrolysis; D007700:Kinetics; D008938:Mitosis; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; C051521:phosphatidylethanol; D011433:Propranolol; D010738:Type C Phospholipases; D010739:Phospholipase D