Inhibition of the action of a stimulatory GDP/GTP exchange protein for smg p21 by acidic membrane phospholipids.
A stimulatory GDP/GTP exchange protein for smg p21 (smg p21 GDS) stimulated the dissociation of GDP from smg p21B. This reaction was inhibited by acidic membrane phospholipids such as phosphatidylinositol, phosphatidylinositol-4-monophosphate, phosphatidylinositol-4,5-bisphosphate, phosphatidic acid, and phosphatidylserine but not by phosphatidylcholine or phosphatidylethanolamine. These acidic phospholipids inhibited the smg p21 GDS action in a manner competitive with both smg p21 GDS and smg p21B. smg p21 GDS has other actions to inhibit the binding of smg p21B to membranes and to induce the dissociation of prebound smg p21B from the membranes. The acidic phospholipids also inhibited these two actions of smg p21 GDS. smg p21B has a polybasic region and an isoprenoid moiety in its C-terminal region which are necessary for its membrane-binding activity and its sensitivity to the smg p21 GDS actions. Therefore, it is possible that acidic membrane phospholipids interact with this polybasic region and thereby inhibit the smg p21 GDS actions.
Kawamura
S
S
Department of Biochemistry, Kobe University School of Medicine.
Kaibuchi
K
K
Hiroyoshi
M
M
Fujioka
H
H
Mizuno
T
T
Takai
Y
Y
D000818:Animals; D002417:Cattle; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008563:Membrane Lipids / Q000494:pharmacology*; D008566:Membranes / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology*; D011506:Proteins / Q000037:antagonists & inhibitors*; D020668:rap GTP-Binding Proteins; D020663:ras Guanine Nucleotide Exchange Factors
D020662:Guanine Nucleotide Exchange Factors; D008563:Membrane Lipids; D010743:Phospholipids; D011506:Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins