Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on Ras.

摘要: Abstract We report the novel finding that Phospholipase D2 (PLD2), through its PX and PH domains, binds specifically to Ras catalyzes GDP/GTP exchange (i.e., is a GEF), with potency comparable Ras-GRF-1, known Ras-GEF. Cells overexpressing PLD2-GEF inactive mutants (F129Y R172C/L173A) fail stimulate cell proliferation compared wild type-expressing cells. The GEF effect on follows faster kinetics than other GTPase substrates (such as Rac2 or Rac1) better substrate, too. action due PLD2 (protein) itself, independent of lipase product PA. PA can still have fine-tuning regulatory Ras-GTP depending upon cellular concentration. Rapidly growing human breast cancer cells MDA-MB 231 (but not slow MCF7 counterpart) high levels endogenous which correlates activation. PLD2-“GEF” activity even higher classical “lipase” abrogated single point mutants, particularly F129Y, concomitantly rate growth. This be crucial biology in only mutations explain abnormal growth, but existence new for Ras: molecule happens phospholipase.