Pancreatic islets express a Ca2+-independent phospholipase A2 enzyme that contains a repeated structural motif homologous to the integral membrane protein binding domain of ankyrin.
Pancreatic islets express a Ca2+-independent phospholipase A2 (CaI-PLA2) activity that is sensitive to inhibition by a haloenol lactone suicide substrate that also attenuates glucose-induced hydrolysis of arachidonic acid from islet phospholipids and insulin secretion. A cDNA has been cloned from a rat islet cDNA library that encodes a protein with a deduced amino acid sequence of 751 residues that is homologous to a CaI-PLA2 enzyme recently cloned from Chinese hamster ovary cells. Transient transfection of both COS-7 cells and Chinese hamster ovary cells with the cloned islet CaI-PLA2 cDNA resulted in an increase in cellular CaI-PLA2 activity, and this activity was susceptible to inhibition by haloenol lactone suicide substrate. The domain of the islet CaI-PLA2 from amino acid residues 150-414 is composed of eight stretches of a repeating sequence motif of approximately 33-amino acid residues in length that is highly homologous to domains of ankyrin that bind both tubulin and integral membrane proteins, including several proteins that regulate ionic fluxes across membranes. These findings complement previous pharmacologic observations that suggest that CaI-PLA2 may participate in regulating transmembrane ion flux in glucose-stimulated beta-cells.
Ma
Z
Z
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ramanadham
S
S
Kempe
K
K
Chi
X S
XS
Ladenson
J
J
Turk
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000235:genetics; D001483:Base Sequence; D016466:CHO Cells; D019556:COS Cells; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D054522:Group VI Phospholipases A2; D006863:Hydrogen-Ion Concentration; D007515:Islets of Langerhans / Q000201:enzymology*; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000096:biosynthesis / Q000235:genetics*; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011753:Pyrones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D017487:Ankyrins; D018076:DNA, Complementary; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; D012333:RNA, Messenger; D011994:Recombinant Proteins; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2