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The Phospholipase A1 Activity of Acyl‐Protein Thioesterase Links Platelet Activation to LPA Production During Blood Clotting
Author(s) -
Bolen Alyssa Lynn,
Naren Anjapravanda P.,
Baker Daniel L.,
BeranovaGiorgianni Sarka,
Best Michael D.,
Rowland Meng M.,
Norman Derek D.,
Chen Li,
Yarlagadda Sunitha,
Sano Takemitsu,
Tsukahara Tamotsu,
Igarashi Yasuyuki,
Tigyi Gabor,
Liliom Karoly
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.551.1
Platelet activation initiates an upsurge in 18:2 and 20:4 lysophosphatidic acid (LPA) production. The biochemical pathway responsible for LPA production during blood clotting is not fully understood. We have purified a phospholipase A 1 (PLA 1 ) from thrombin‐activated human platelets using sequential chromatographic steps followed by fluorophosphonate‐biotin affinity labeling and proteomics. We identified acyl‐protein thioesterase 1 (aka. lysophospholipase A 1 , accession code O75608 ) as a novel PLA 1 . Addition of this recombinant PLA 1 significantly increased the production of sn ‐2‐esterified polyunsaturated LPCs and the corresponding LPAs in plasma. We next examined the regioisomeric preference of lysophospholipase D/autotaxin (ATX), which is the subsequent step in LPA production. To prevent acyl‐migration regioisomers of oleyl‐ sn ‐glycero‐3‐phosphocholine (LPAF) were synthesized. ATX preferred the sn ‐1 over the sn ‐2 regioisomer of LPAF. We propose the following LPA production pathway in blood: 1) Activated platelet secrete PLA 1 . 2) PLA 1 generates a pool of sn‐2 lysophospholipids. 3) These newly generated sn‐2 lysophospholipids undergo acyl migration to yield sn‐1 lysophospholipids, which are the preferred substrates of ATX. 4) ATX cleaves the sn‐1 lysophospholipids to generate sn‐1 LPA species predominant with 18:2 and 20:4 fatty acids.