PMID- 10366595
OWN - NLM
STAT- MEDLINE
DCOM- 19990712
LR  - 20201209
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 145
IP  - 6
DP  - 1999 Jun 14
TI  - Role of phosphorylation sites and the C2 domain in regulation of cytosolic
      phospholipase A2.
PG  - 1219-32
AB  - Cytosolic phospholipase A2 (cPLA2) mediates agonist-induced arachidonic acid
      release, the first step in eicosanoid production. cPLA2 is regulated by
      phosphorylation and by calcium, which binds to a C2 domain and induces its
      translocation to membrane. The functional roles of phosphorylation sites and the 
      C2 domain of cPLA2 were investigated. In Sf9 insect cells expressing cPLA2,
      okadaic acid, and the calcium-mobilizing agonists A23187 and CryIC toxin induce
      arachidonic acid release and translocation of green fluorescent protein
      (GFP)-cPLA2 to the nuclear envelope. cPLA2 is phosphorylated on multiple sites in
      Sf9 cells; however, only S505 phosphorylation partially contributes to cPLA2
      activation. Although okadaic acid does not increase calcium, mutating the
      calcium-binding residues D43 and D93 prevents arachidonic acid release and
      translocation of cPLA2, demonstrating the requirement for a functional C2 domain.
      However, the D93N mutant is fully functional with A23187, whereas the D43N mutant
      is nearly inactive. The C2 domain of cPLA2 linked to GFP translocates to the
      nuclear envelope with calcium-mobilizing agonists but not with okadaic acid.
      Consequently, the C2 domain is necessary and sufficient for translocation of
      cPLA2 to the nuclear envelope when calcium is increased; however, it is required 
      but not sufficient with okadaic acid.
FAU - Gijon, M A
AU  - Gijon MA
AD  - Division of Basic Science, Department of Pediatrics, National Jewish Medical and 
      Research Center, Denver, Colorado 80206, USA.
FAU - Spencer, D M
AU  - Spencer DM
FAU - Kaiser, A L
AU  - Kaiser AL
FAU - Leslie, C C
AU  - Leslie CC
LA  - eng
GR  - P01 HL034303/HL/NHLBI NIH HHS/United States
GR  - HL61378/HL/NHLBI NIH HHS/United States
GR  - HL34303/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Bacillus thuringiensis Toxins)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Endotoxins)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (insecticidal crystal protein, Bacillus Thuringiensis)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 526U7A2651 (Egtazic Acid)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Bacillus thuringiensis Toxins
MH  - Bacterial Proteins/pharmacology
MH  - *Bacterial Toxins
MH  - Binding Sites
MH  - Calcimycin/pharmacology
MH  - Calcium/metabolism/pharmacology
MH  - Cell Line
MH  - Cytosol/drug effects/*enzymology/metabolism
MH  - Egtazic Acid/pharmacology
MH  - Endotoxins/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Green Fluorescent Proteins
MH  - Hemolysin Proteins
MH  - Insecta
MH  - Luminescent Proteins
MH  - Nuclear Envelope/drug effects/metabolism
MH  - Okadaic Acid/pharmacology
MH  - Peptide Fragments/chemistry/genetics/metabolism
MH  - Phospholipases A/chemistry/genetics/*metabolism
MH  - Phospholipases A2
MH  - Phosphorylation
MH  - Recombinant Fusion Proteins/biosynthesis/metabolism
PMC - PMC2133140
EDAT- 1999/06/15 00:00
MHDA- 1999/06/15 00:01
CRDT- 1999/06/15 00:00
PHST- 1999/06/15 00:00 [pubmed]
PHST- 1999/06/15 00:01 [medline]
PHST- 1999/06/15 00:00 [entrez]
AID - 10.1083/jcb.145.6.1219 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Jun 14;145(6):1219-32. doi: 10.1083/jcb.145.6.1219.