PLD2 has both enzymatic and cell proliferation-inducing capabilities, that are differentially regulated by phosphorylation and dephosphorylation.

摘要: Phospholipase D2 (PLD2) overexpression in mammalian cells results cell transformation. We have hypothesized that this is due to an increase of de novo DNA synthesis. show here PLD2-WT leads increased synthesis, as measured by the expression levels proliferation markers PCNA, p27{sup KIP1} and phospho-histone-3. The enhancing effect was even higher with phosphorylation-deficient PLD2-Y179F PLD2-Y511F mutants. mechanism for did not involve enzymatic activity lipase, but, rather, presence protein tyrosine phosphatase CD45, silencing siRNA CD45 abrogated effect. two Y{yields}F mutants had common a YxN consensus site that, phosphorylated counterparts, could be recognized SH2-bearing proteins, such Grb2. Even though Y179F Y511F cannot bind Grb2, they still find other partners, one which, we reasoned, itself. Affinity purified PLD2 indeed activated Grb2 deactivated vitro. concluded PLD2, aided mediates lipase activity, whereas dephosphorylated induction proliferation, specific residues involved newly discovered regulation are Y{sup 179} 511}.