PMID- 27118725
OWN - NLM
STAT- MEDLINE
DCOM- 20180816
LR  - 20240324
IS  - 1520-6882 (Electronic)
IS  - 0003-2700 (Print)
IS  - 0003-2700 (Linking)
VI  - 88
IP  - 10
DP  - 2016 May 17
TI  - Multistep Compositional Remodeling of Supported Lipid Membranes by Interfacially 
      Active Phosphatidylinositol Kinases.
PG  - 5042-5
LID - 10.1021/acs.analchem.6b01293 [doi]
AB  - The multienzyme catalytic phosphorylation of phosphatidylinositol (PI) in a 
      supported lipid membrane platform is demonstrated for the first time. One-step 
      treatment with PI 4-kinase IIIbeta (PI4Kbeta) yielded PI 4-phosphate (PI4P), while a 
      multistep enzymatic cascade of PI4Kbeta followed by PIP 5-kinase produced 
      PI-4,5-bisphosphate (PI(4,5)P2 or PIP2). By employing quartz crystal microbalance 
      with dissipation monitoring, we were able to track membrane association of kinase 
      enzymes for the first time as well as detect PI4P and PI(4,5)P2 generation based 
      on subsequent antibody binding to the supported lipid bilayers. Pharmacologic 
      inhibition of PI4Kbeta by a small molecule inhibitor was also quantitatively 
      assessed, yielding an EC50 value that agrees well with conventional biochemical 
      readout. Taken together, the development of a PI-containing supported membrane 
      platform coupled with surface-sensitive measurement techniques for kinase studies 
      opens the door to exploring the rich biochemistry and pharmacological targeting 
      of membrane-associated phosphoinositides.
FAU - Tabaei, Seyed R
AU  - Tabaei SR
AD  - School of Materials Science and Engineering and Centre for Biomimetic Sensor 
      Science, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.
FAU - Guo, Feng
AU  - Guo F
AD  - Departments of Medicine, Division of Gastroenterology and Hepatology, and 
      Microbiology & Immunology, Stanford University School of Medicine , Stanford, 
      California 94305, United States.
FAU - Rutaganira, Florentine U
AU  - Rutaganira FU
AD  - Howard Hughes Medical Institute, Department of Cellular and Molecular 
      Pharmacology, University of California San Francisco , San Francisco, California 
      94158-2280, United States.
FAU - Vafaei, Setareh
AU  - Vafaei S
AD  - School of Materials Science and Engineering and Centre for Biomimetic Sensor 
      Science, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.
FAU - Choong, Ingrid
AU  - Choong I
AD  - Departments of Medicine, Division of Gastroenterology and Hepatology, and 
      Microbiology & Immunology, Stanford University School of Medicine , Stanford, 
      California 94305, United States.
FAU - Shokat, Kevan M
AU  - Shokat KM
AD  - Howard Hughes Medical Institute, Department of Cellular and Molecular 
      Pharmacology, University of California San Francisco , San Francisco, California 
      94158-2280, United States.
FAU - Glenn, Jeffrey S
AU  - Glenn JS
AD  - Departments of Medicine, Division of Gastroenterology and Hepatology, and 
      Microbiology & Immunology, Stanford University School of Medicine , Stanford, 
      California 94305, United States.
AD  - Palo Alto Veterans Administration Medical Center , Palo Alto, California 94304, 
      United States.
FAU - Cho, Nam-Joon
AU  - Cho NJ
AD  - School of Materials Science and Engineering and Centre for Biomimetic Sensor 
      Science, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.
LA  - eng
GR  - R01 AI099245/AI/NIAID NIH HHS/United States
GR  - T32 GM064337/GM/NIGMS NIH HHS/United States
GR  - U19 AI109662/AI/NIAID NIH HHS/United States
PT  - Letter
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160428
PL  - United States
TA  - Anal Chem
JT  - Analytical chemistry
JID - 0370536
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipid Bilayers)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (phosphatidylinositol 4-phosphate)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase)
RN  - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase)
SB  - IM
MH  - 1-Phosphatidylinositol 4-Kinase/antagonists & inhibitors/*chemistry
MH  - Enzyme Inhibitors/chemistry
MH  - Lipid Bilayers/*chemistry
MH  - Membrane Proteins/antagonists & inhibitors/*chemistry
MH  - Phosphatidylinositol 4,5-Diphosphate/chemistry
MH  - Phosphatidylinositol Phosphates/chemistry
MH  - Phosphotransferases (Alcohol Group Acceptor)/*chemistry
MH  - Quartz Crystal Microbalance Techniques
PMC - PMC5291064
MID - NIHMS843666
EDAT- 2016/04/28 06:00
MHDA- 2018/08/17 06:00
PMCR- 2017/02/03
CRDT- 2016/04/28 06:00
PHST- 2016/04/28 06:00 [entrez]
PHST- 2016/04/28 06:00 [pubmed]
PHST- 2018/08/17 06:00 [medline]
PHST- 2017/02/03 00:00 [pmc-release]
AID - 10.1021/acs.analchem.6b01293 [doi]
PST - ppublish
SO  - Anal Chem. 2016 May 17;88(10):5042-5. doi: 10.1021/acs.analchem.6b01293. Epub 
      2016 Apr 28.