The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases.
Numerous inositol polyphosphate 5-phosphatases catalyze the degradation of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P(2)) to phosphatidylinositol-4-phosphate (PtdIns-4-P). An alternative pathway to degrade PtdIns-4,5-P(2) is the hydrolysis of PtdIns-4,5-P(2) by a 4-phosphatase, leading to the production of PtdIns-5-P. Whereas the bacterial IpgD enzyme is known to catalyze this reaction, no such mammalian enzyme has been found. We have identified and characterized two previously undescribed human enzymes, PtdIns-4,5-P(2) 4-phosphatase type I and type II, which catalyze the hydrolysis of PtdIns-4,5-P(2) to phosphatidylinositol-5-phosphate (PtdIns-5-P). Both enzymes are ubiquitously expressed and localize to late endosomal/lysosomal membranes in epithelial cells. Overexpression of either enzyme in HeLa cells increases EGF-receptor degradation upon EGF stimulation.
Ungewickell
Alexander
A
Division of Hematology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hugge
Christopher
C
Kisseleva
Marina
M
Chang
Shao-Chun
SC
Zou
Jun
J
Feng
Yucheng
Y
Galyov
Edouard E
EE
Wilson
Monita
M
Majerus
Philip W
PW
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D016957:Burkholderia pseudomallei / Q000378:metabolism; D019556:COS Cells; D002384:Catalysis; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D000072181:Inositol Polyphosphate 5-Phosphatases; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry* / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000737:chemistry; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D000099182:Phosphoinositide 5-Phosphatases
D018076:DNA, Complementary; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D000072181:Inositol Polyphosphate 5-Phosphatases; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000099182:Phosphoinositide 5-Phosphatases; C037178:phosphatidylinositol 4-phosphate