Lipid phosphate phosphatase-1 dephosphorylates exogenous lysophosphatidate and thereby attenuates its effects on cell signalling.
The serum-derived phospholipid growth factor, lysophosphatidate (LPA), activates cells through a family of G-protein-coupled EDG receptors. The present article examines the role of lipid phosphate phosphatase-1 (LPP-1, or phosphatidate phosphate 2A) in regulating cell activation by LPA. Overexpressing LPP-1 approximately doubled the rate of dephosphorylation of exogenous LPA by Rat2 fibroblasts. The amount of LPA dephosphorylation was restricted to less than 10% of the total exogenous LPA. Over-expression of LPP-1 attenuated cell activation as indicated by diminished responses including cAMP, Ca2+, activation of phospholipase D and ERK, DNA synthesis and cell division. LPP-1 therefore provides a novel level of regulation for controlling cell signalling by exogenous LPA.
Pilquil
C
C
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Singh
I
I
Zhang
Q X
QX
Ling
Z C
ZC
Buri
K
K
Stromberg
L M
LM
Dewald
J
J
Brindley
D N
DN
D000818:Animals; D008246:Lysophospholipids / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D008246:Lysophospholipids; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D014157:Transcription Factors; C112948:lipid phosphate phosphatase; D010711:Phosphatidate Phosphatase