Receptor-binding capability of pancreatic phospholipase A2 is separable from its enzymatic activity.
Mammalian pancreatic phospholipase A2 (PLA2-I) has its specific receptor through which PLA2-I induces a variety of biological responses. In this study, a fundamental relationship between the enzymatic and the receptor-binding activities of PLA2-I was investigated. The specific binding of PLA2-I to the receptor was found to be independent of Ca2+ which is requisite for the PLA2 activity. On the basis of this observation, we designed and produced mutant PLA2-Is without Ca(2+)-binding abilities in order to demonstrate that the structural requirement for the enzymatic activity of PLA2-I is not identical with that for its receptor-binding reaction. These mutant PLA2-Is lost almost all enzymatic activity through a disturbance at the Ca(2+)-binding site, as expected, but still retained a substantial affinity to the receptor, allowing us to conclude that the receptor-binding reaction of PLA2-I is separable from its catalytic action.
Ishizaki
J
J
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kishino
J
J
Teraoka
H
H
Ohara
O
O
Arita
H
H
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010179:Pancreas / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D054507:Receptors, Phospholipase A2; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D006023:Glycoproteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium