Mammalian carboxylesterase (CES) releases GPI-anchored proteins from the cell surface upon lipid raft fluidization.
Mammalian carboxylesterase (CES) is well known as a biotransformation enzyme for prodrugs and xenobiotics. Here, we purified CES as a GPI-anchored protein (GPI-AP)-releasing factor (GPIase) that releases such protein from the cell surface. All five isoforms of CES showed this activity to various degrees. When the serine residue of the catalytic triad for esterase was replaced by alanine, esterase activity was completely disrupted, while full GPIase activity remained, suggesting that these two activities are exhibited via different mechanisms. CES6, a new class of mammalian CES, exhibited the highest GPIase activity and released specific GPI-APs from the cell surface after lipid raft fluidization. The released product contained a GPI component, indicating that GPI-AP was released by cleavage in GPI. These results revealed for the first time that CES recognizes and catalyzes macromolecule GPI-AP as well as small molecules.
Laboratory of Animal Experiments for Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Syogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Kaoru
K
Orihashi
Hiromasa
H
Tojo
Katsuya
K
Okawa
Yuko
Y
Tashima
Takashi
T
Morita
Gen
G
Kondoh
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D043182:Carboxylesterase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D058851:GPI-Linked Proteins / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D017354:Point Mutation; D020033:Protein Isoforms / Q000378:metabolism; D011817:Rabbits
D058851:GPI-Linked Proteins; D007527:Isoenzymes; D020033:Protein Isoforms; D043182:Carboxylesterase; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental