title: AP180 binds to the C-terminal SH2 domain of phospholipase C-gamma1 and inhibits its enzymatic activity.
abstract: The role of phospholipase Cgamma1 (PLCgamma1) in signal transduction was investigated by characterizing its SH domain-binding proteins that may represent components of a novel signaling pathway. A 180-kDa protein that binds to the SH2 domain of PLCgamma1 was purified from rat brain. The amino acid sequence of peptide derived from the purified protein is now identified as AP180, a clathrin assembly protein that has been implicated in clathrin-mediated synaptic vesicle recycling in synapses. In this report, we demonstrate the stable association of PLCgamma1 with AP180 in a clathrin-coated vesicle complex, which not only binds to the carboxyl-terminal SH2 domain of PLCgamma1, but also inhibits its enzymatic activity in a dose-dependent manner.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Hong
authors.forename: Sang Dai
authors.initials: SD
authors.lastname: Park
authors.forename: Chul Geun
authors.initials: CG
authors.lastname: Kim
authors.forename: Min Dong
authors.initials: MD
authors.lastname: Song
authors.forename: Tae Kyu
authors.initials: TK
authors.lastname: Park
authors.forename: Chan Gil
authors.initials: CG
authors.lastname: Kim
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D010455:Peptides / Q000737:chemistry; D051966:Phospholipase C gamma; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D018909:src Homology Domains
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002966:Clathrin; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C439023:clathrin assembly protein AP180; D005982:Glutathione Transferase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma