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E-grāmata: Inositol Phospholipid Metabolism and Phosphatidyl Inositol Kinases

Edited by (Banting and Best Department of Medical Research, University of Toronto, Canada)
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Inositol Phospholipid Metabolism and Phosphatidyl Inositol KinasesPalielināt
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This book offers a wide ranging and review of cutting edge developments along with tried and tested methods for isolation, resolution and quantification of inositol phospholipids and inositol polyphosphates in both cells and tissues. It includes detailed and rigorous methodology for identification of molecular species of inositol phospholipids, including their phosphates and glycans, with numerous examples of specific applications.



Wherever available, both chromatographic and mass spectrometric
evidence is presented for specific phospholipid involvement in the biochemical transformations accompanying metabolic signalling events and, where possible, controversies have been resolved on basis of analytical ambiguity. The review of the lipid
analyses extends to products of phosphatidylinositol kinases, phosphatases and lipases.



A general review chapter is included on metabolic signalling with special emphasis on the lipid products of 3-kinases. In view of the general lack of commercially available standards for inositol phospholipids and inositol phosphates, the book concludes with a chapter on the preparation and collection of chromatographic and mass spectrometric proof of their purity and identity.

This book complements recent books and reviews on the mechanisms metabolic signalling, receptor binding and the polypeptide structure of the proteins involved in the various signalling pathways. It also complements those texts that deal exclusively with the chemical synthesis of the phosphatidylinositols and their polyphosphates and glycans.

Recenzijas

"In this excellent new book, Kuksis shows how our knowledge of the remarkable activities of these compounds has only been possible because of the continuous development of novel analytical methodologies...In short, it is hard to conceive of a more comprehensive and thorough guide to the subject of analysis and biochemistry of phosphatidylinositol and its metabolites. It is quite remarkable that this substantial book has been produced by single author, especially as this leads to a uniformity of treatment in the various chapters impossible to achieve in multi-author volumes. Every biochemistry and lipid library should have a copy." --William W. Christie, MRS Lipid Analysis Unit, Scottish Crop research Institute, Invergowrie, Dundee, Scotland for LIPID TECHNOLOGY NEWSLETTER, December 2003

Preface v
Abbreviations xxiii
Chapter
1. General Introduction		 1(36)
1.1. Introduction
1(5)
1.2. Natural occurrence
6(3)
1.2.1. Phosphatidylinositol
6(1)
1.2.2. Phosphatidylinositol phosphates
7(1)
1.2.3. Inositol phosphates
7(1)
1.2.4. Glycosyl phosphatidylinositols
8(1)
1.3. Biological significance
9(5)
1.3.1. Structural components
9(1)
1.3.2. Signaling molecules
10(3)
1.3.3. Metabolic intermediates
13(1)
1.4. Nomenclature
14(19)
1.4.1. Inositol glycerophospholipids
15(4)
1.4.1.1. Lipid components
15(1)
1.4.1.2. Stereoisomers of glycerolipids
16(3)
1.4.1.3. Positional isomers
19(1)
1.4.2. Inositol and phosphatidylinositol phosphates
19(11)
1.4.2.1. Stereoisomers of inositols
20(4)
1.4.2.2. Numbering of phosphate groups
24(6)
1.4.3. Inositol pyrophosphates
30(1)
1.4.4. Kinases, phosphatases and phospholipases
31(2)
1.4.5. Other conventions
33(1)
1.5. Scope of the book
33(4)
Chapter
2. Phosphatidylinositols		 37(70)
2.1. Isolation
37(11)
2.1.1. Solvent extraction
37(5)
2.1.1.1. Chloroform/methanol
38(2)
2.1.1.2. Other solvents
40(2)
2.1.2. Solid phase extraction
42(6)
2.1.2.1. TLC and HPTLC
42(3)
2.1.2.2. HPLC
45(2)
2.1.2.3. Cartridge extraction
47(1)
2.2. Identification
48(48)
2.2.1. Determination of structure
49(17)
2.2.1.1. Chemical methods
50(4)
2.2.1.2. Enzymic methods
54(5)
2.2.1.3. Mass spectrometric methods
59(3)
2.2.1.4. NMR
62(4)
2.2.2. Composition of fatty acids
66(4)
2.2.2.1. Total
66(1)
2.2.2.2, sn-l-position
66(2)
2.2.2.3. sn-2-position
68(2)
2.2.3. Determination of molecular species
70(26)
2.2.3.1. Intact PtdIns
70(9)
2.2.3.2. PtdOH
79(4)
2.2.3.3. Diradylglycerols
83(12)
2.2.3.4. Inositol isomers
95(1)
2.3. Quantification
96(11)
2.3.1. Intact PtdIns
98(1)
2.3.2. Diacylglycerols
99(2)
2.3.3. Fatty acids
101(1)
2.3.4. Inositol
101(4)
2.3.5. Phosphorus
105(2)
Chapter
3. Phosphatidylinositol Phosphates		 107(68)
3.1. Isolation
107(21)
3.1.1. Solvent extraction
107(4)
3.1.2. Solid phase extraction (cartridge)
111(17)
3.1.2.1. TLC and HPTLC
111(10)
3.1.2.2. HPLC
121(5)
3.1.2.3. Ion exchange
126(1)
3.1.2.4. Affinity chromatography
127(1)
3.2. Determination of structure
128(23)
3.2.1. Chemical methods
129(3)
3.2.1.1. General assays
129(1)
3.2.1.2. Deacylation
130(1)
3.2.1.3. Deglyceration
130(2)
3.2.1.4. Dephosphorylation
132(1)
3.2.2. Enzymic methods
132(3)
3.2.2.1. Phospholipases
132(1)
3.2.2.2. Phosphatases
133(1)
3.2.2.3. Kinases
133(1)
3.2.2.4. Polyol dehydrogenase
134(1)
3.2.3. Chromatographic methods
135(6)
3.2.3.1. Resolution of intact PtdInsPs
135(1)
3.2.3.2. Resolution of GroPInsPs
136(5)
3.2.3.3. Resolution of lnsPs
141(1)
3.2.3.4. Resolution of isomeric Ins
141(1)
3.2.4. Mass spectrometric methods
141(10)
3.2.4.1. FAB/MS
142(1)
3.2.4.2. ES/MS/MS
143(5)
3.2.4.3. MALDI-TOF/MS
148(3)
3.3. Resolution of molecular species
151(11)
3.3.1. Intact PtdInsPs and PtdIns
153(5)
3.3.2. Phosphatidic acids
158(1)
3.3.3. Diacylglycerols
158(1)
3.3.4. Positional distribution of fatty acids
159(3)
3.3.5. Inositol isomers
162(1)
3.4. Quantification
162(13)
3.4.1. MS/MS
163(2)
3.4.2. Autoradiography
165(2)
3.4.3. Radioreceptor assay
167(4)
3.4.4. Other methods
171(4)
Chapter
4. Inositol Phosphates		 175(78)
4.1. Introduction
175(1)
4.2. Isolation
176(3)
4.2.1. Acid extraction
176(2)
4.2.2. Removal of nucleotides
178(1)
4.2.3. Neutralization of acid extracts
178(1)
4.3. Resolution of chemical families
179(12)
4.3.1. TLC
180(2)
4.3.2. Anion exchange cartridge chromatography
182(3)
4.3.3. HPLC analysis
185(5)
4.3.4. Other
190(1)
4.4. Resolution of positional isomers
191(16)
4.4.1. Inositol monophosphates (InsP1s)
194(1)
4.4.2. Inositol bisphosphates (InsP2s)
195(1)
4.4.3. Inositol trisphosphates (InsP3s)
196(2)
4.4.4. Inositol tetrakisphosphates (InsP4s)
198(2)
4.4.5. Inositol pentakisphosphates (InsP5s)
200(5)
4.4.6. Inositol hexakis and pyrophosphates (InsP6s, InsP7s and InsP8s)
205(2)
4.5. Determination of chemical structure
207(16)
4.5.1. Chemical analysis
207(5)
4.5.2. Nuclear magnetic resonance spectroscopy (NMR)
212(5)
4.5.3. Mass spectrometry
217(6)
4.6. Determination of stereochemical structure
223(12)
4.6.1. Optical rotation
224(1)
4.6.2. Polyol dehydrogenases
224(8)
4.6.3. Inositol phosphate kinases
232(1)
4.6.4. Inositol phosphate phosphatases
233(2)
4.7. Quantification
235(18)
4.7.1. Radio-isotope assays
236(3)
4.7.2. Radio-receptor assays
239(4)
4.7.3. Mass assays of inositol phosphates
243(10)
Chapter
5. Glycosylphosphatidylinositols		 253(82)
5.1. Introduction
253(1)
5.2. Natural occurrence and isolation
254(13)
5.2.1. Isolation of free glycosyl PtdIns-anchors
255(4)
5.2.1.1. Extraction
256(2)
5.2.1.2. Purification
258(1)
5.2.2. Isolation of glycosyl PtdIns-anchored proteins
259(4)
5.2.2.1. Metabolic labeling
260(2)
5.2.2.2. Chemical labeling
262(1)
5.2.3. Release of bound glycosyl PtdIns-anchors
263(4)
5.2.3.1. Proteolysis
264(2)
5.2.3.2. Nitrous acid deamination
266(1)
5.2.3.3. Hydrofluoric acid
267(1)
5.3. Determination of chemical structure
267(40)
5.3.1. Protein-ethanolamine bridge
271(8)
5.3.2. Glucosamine-inositol linkage
279(1)
5.3.3. Glycan moiety
280(8)
5.3.4. PtdIns moiety
288(6)
5.3.5. Diradylglycerol moiety
294(8)
5.3.6. Composition of fatty chains
302(5)
5.3.7. Inositol moiety
307(1)
5.4. Determination of molecular species
307(15)
5.4.1. Mass spectrometry
308(3)
5.4.1.1. Intact protein
308(2)
5.4.1.2. Intact glycosyl PtdIns
310(1)
5.4.1.3. PtdIns moiety
311(1)
5.4.2. Chromatography/mass spectrometry
311(11)
5.4.2.1. Intact glycosyl PtdIns
311(1)
5.4.2.2. Diradyl GroPIns
312(1)
5.4.2.3. Diradyl GroPOH
313(2)
5.4.2.4. Diradylglycerols
315(7)
5.5. Quantification
322(4)
5.5.1. Mass spectrometry
323(1)
5.5.2. Chromatography
324(2)
5.5.3. Chemical analysis
326(1)
5.6. Related structures
326(9)
5.6.1. Glycosylinositol phosphoceramides
326(4)
5.6.2. Lipophosphoglycans and glycoinositolphospholipids
330(1)
5.6.3. Lipoarabinomannans and arabinogalactans
331(4)
Chapter
6. Biosynthesis of Inositol Phospholipids		 335(68)
6.1. Introduction
335(1)
6.2. Phosphatidylinositols
336(16)
6.2.1. De novo synthesis
336(9)
6.2.1.1. Synthesis of CPD-DAG via CTP
341(2)
6.2.1.2. Synthesis of PtdIns via CPD-DAG
343(1)
6.2.1.3. Synthesis of PtdIns via CPD-DAG in plants
344(1)
6.2.2. Remodeling
345(7)
6.2.2.1. Acyl group exchange
345(3)
6.2.2.2. Head-group exchange
348(4)
6.3. Phosphatidylinositol phosphates
352(24)
6.3.1. PtdIns monophosphates
353(12)
6.3.1.1. PtdIns(4)P
354(5)
6.3.1.2. PtdIns(3)P
359(4)
6.3.1.3. PtdIns(5)P
363(2)
6.3.2. PtdIns bisphosphates
365(8)
6.3.2.1. PtdIns(4,5)P2
366(3)
6.3.2.2. PtdIns(3,4)P2
369(2)
6.3.2.3. PtdIns(3,5)P2
371(2)
6.3.3. PtdIns trisphosphates
373(3)
6.3.3.1. PtdIns(3,4,5)P3
373(3)
6.4. Glycosyl phosphatidylinositols
376(27)
6.4.1. GPtdlns protein anchors
377(21)
6.4.1.1. GlcNAc-PtdIns
379(3)
6.4.1.2. GlcN-PtdIns
382(2)
6.4.1.3. GlcN-PtdIns acyl esters
384(1)
6.4.1.4. GlcN-PtdIns mannosides
385(3)
6.4.1.5. GlcN-PtdIns(Man)3EtnP
388(2)
6.4.1.6. Transfer to protein
390(1)
6.4.1.7. Remodeling
391(7)
6.4.2. Protein-free GPtdlns
398(6)
6.4.2.1. Protozoal GPtdlns-related structures
399(1)
6.4.2.2. Lipophosphoglycans
400(1)
6.4.2.3. Glycoinositolphospholipids (GIPLs)
401(1)
6.4.2.4. Glucosyl PtdIns glycolipids
401(2)
Chapter
7. Phosphatidylinositol and Inositol Phosphate Kinases		 403(60)
7.1. Introduction
403(1)
7.2. Phosphatidylinositol kinases
404(19)
7.2.1. PtdIns 3-kinase
407(5)
7.2.1.1. Assay of immunoprecipitates
408(3)
7.2.1.2. Assay of cell lysates
411(1)
7.2.2. PtdIns 4-kinases
412(7)
7.2.2.1. Assays in micelles
416(1)
7.2.2.2. Assays of recombinant proteins
417(1)
7.2.2.3. Plant tissue assays
418(1)
7.2.3. Ptdlns 5-kinases
419(4)
7.2.3.1. Assays of cellular proteins
420(2)
7.2.3.2. Assays of recombinant protein
422(1)
7.3. Phosphatidylinositol monophosphate kinases
423(11)
7.3.1. PtdInsP 3-kinases
424(3)
7.3.1.1. Ptdlns(4)P 3-kinase
425(1)
7.3.1.2. PtdIns(5)P 3-kinase
426(1)
7.3.2. PtdInsP 4-kinases
427(3)
7.3.2.1. PtdIns(3)P 4-kinase
427(1)
7.3.2.2. PtdIns(5)P 4-kinase
428(2)
7.3.3. PtdInsP 5-kinases
430(4)
7.3.3.1. PtdIns(3)P 5-kinase
430(2)
7.3.3.2. PtdIns(4)P 5-kinase
432(2)
7.4. Phosphatidylinositol bisphosphate kinases
434(5)
7.4.1. PtdIns (4,5)P2 3-kinase
434(3)
7.4.2. PtdIns(3,5)P2 4-kinase
437(1)
7.4.3. Ptdlns(3,4)P2 5-kinase
437(2)
7.5. Inositol monophosphate kinases
439(1)
7.5.1. InsP 1-kinases
439(1)
7.5.1.1. Ins(3)P 1-kinase
439(1)
7.5.2. InsP 6-kinases
440(1)
7.5.2.1. Ins(3)P 6-kinases
440(1)
7.5.2.2. Ins(2)P 6-kinases
440(1)
7.6. Inositol bisphosphate kinases
440(2)
7.6.1. InsP2 4-kinases
441(1)
7.6.1.1. Ins(3,6)P2 4-kinases
441(1)
7.6.2. InsP2 5-kinases
441(1)
7.6.2.1. Ins(1,3)P2 5-kinase
441(1)
7.6.2.2. Ins(2,6)P2 5-kinase
441(1)
7.6.3. InsP2 6/3-kinase
441(1)
7.7. Inositol tisphosphate kinases
442(8)
7.7.1. InsP3 1-kinases
442(1)
7.7.1.1. Ins(3,4,6)P31-kinase
442(1)
7.7.2. InsP3 3-kinases
442(3)
7.7.2.1. Ins(1,4,5)P3 3-kinase
442(3)
7.7.2.2. Ins(2,5,6)P3 3-kinase
445(1)
7.7.3. InsP3 6/3 kinases
445(3)
7.7.3.1. Ins(1,4,5)P3 6/3-kinase
445(3)
7.7.4. InsP3 6/5 kinase
448(2)
7.7.4.1. Ins(1,3,4)P3 6/5-kinase
448(2)
7.7.5. Ins(1,3,5)P3 6-kinase
450(1)
7.8. Inositol tetrakisphosphate kinases
450(3)
7.8.1. InsP4 1-kinases
450(2)
7.8.1.1. Ins(3,4,5,6)P4 1-kinase
450(2)
7.8.2. InsP4 2/4 kinases
452(1)
7.8.2.1. Ins(1,3,5,6)P4 2/4-kinase
452(1)
7.8.3. InsP4 3-kinases
452(1)
7.8.4. InsP4 4-kinases
452(1)
7.8.4.1. Ins(2,3,5,6)P4 4-kinase
452(1)
7.8.5. InsP4 5-kinases
452(1)
7.8.5.1. Ins(1,3,4,6)P4 5-kinase
452(1)
7.9. Inositol pentakisphosphate kinases
453(4)
7.9.1. InsP5 1-kinases
453(1)
7.9.1.1. Ins(2,3,4,5,6)P5 1-kinase
453(1)
7.9.2. InsP5 2-kinases
454(3)
7.9.2.1. Ins(1,3,4,5,6)P5 2-kinase
454(3)
7.9.3. InsP5 3-kinases
457(1)
7.9.3.1. Ins(1,2,4,5,6)P5 3-kinase
457(1)
7.9.4. InsP5 5/6 kinases
457(1)
7.9.4.1. D/t-Ins(1,2,3,4,6)P5 5/6-kinase (Stephens et al., 1991)
457(1)
7.9.5. InsP5 pyrophosphokinase
457(1)
7.9.5.1. Ins(1,3,4,5,6)P5 pyrophosphokinase
457(1)
7.10. Inositol hexakisphosphate kinases
457(6)
7.10.1. InsP6 5-kinase
458(3)
7.10.2. PP-InsP4 kinase
461(1)
7.10.3. bis-PP-InsP4
462(1)
Chapter
8. Phosphatidylinositol Phosphate and Inositol Phosphate Phosphatases		 463(78)
8.1. Introduction
463(2)
8.2. PtdIns phosphate phosphatases
465(32)
8.2.1. PtdIns monophosphate phosphatases
465(9)
8.2.1.1. PtdIns (3)P 3-phosphatase
465(7)
8.2.1.2. PtdIns(4)P 4-phosphatase
472(2)
8.2.1.3. PtdIns(5)P 5-phosphatase
474(1)
8.2.2. PtdIns bisphosphate phosphatases
474(9)
8.2.2.1. PtdInsP2 3-phosphatases
474(1)
8.2.2.2. PtdInsP2 4-phosphatases
475(3)
8.2.2.3. PtdInsP2 5-phosphatases
478(5)
8.2.3. PtdIns tisphosphate phosphatases
483(14)
8.2.3.1. PtdInsP3 3-phosphatases
484(5)
8.2.3.2. PtdInsP3 4-phosphatases
489(1)
8.2.3.3. PtdInsP3 5-phosphatases
490(7)
8.3. Inositol phosphate phosphatases
497(40)
8.3.1. Inositol monophosphate phosphatases
497(7)
8.3.1.1. Ins(1)P phosphatases
497(5)
8.3.1.2. Ins(3)P phosphatases
502(2)
8.3.2. Inositol bisphosphate phosphatases
504(6)
8.3.2.1. InsP2 1-phosphatase
505(1)
8.3.2.2. InsP2 3-phosphatases
506(2)
8.3.2.3. InsP2 4-phosphatase
508(2)
8.3.2.4. InsP2 5-phosphatases
510(1)
8.3.3. Inositol trisphosphate phosphatases
510(16)
8.3.3.1. InsP3 1-phosphatase
511(2)
8.3.3.2. InsP3 3-phosphatases
513(1)
8.3.3.3. InsP3 4-phosphatases
514(2)
8.3.3.4. InsP3 5-phosphatases
516(10)
8.3.4. Inositol tetrakisphosphate phosphatases
526(2)
8.3.4.1. InsP4 3-phosphatases
526(1)
8.3.4.2. InsP4 4-phosphatases
526(1)
8.3.4.3. InsP4 5-phosphatases
527(1)
8.3.5. Inositol pentakisphosphate phosphatases
528(3)
8.3.5.1. InsP51-phosphatases
528(1)
8.3.5.2. InsP5 3-phosphatases
529(2)
8.3.5.3. Ins(1,3,4,5,6)P5 6-phosphatases
531(1)
8.3.6. Inositol hexakisphosphate phosphatases
531(3)
8.3.6.1. InsP6 6-phytase
532(1)
8.3.6.2. InsP6 3-phytase
532(1)
8.3.6.3. InsP6 5-phytase
533(1)
8.3.7. Inositol pyrophosphate phosphatases
534(3)
8.3.7.1. (PP)2InsP4 pyrophosphatase
534(2)
8.3.7.2. PPInsP5 pyrophosphatases
536(1)
8.4. Other phosphatases and phytases
537(4)
8.4.1. Alkaline phosphatases
537(2)
8.4.2. Acid phosphatases
539(1)
8.4.3. Bacillus phytases
540(1)
Chapter
9. Phosphatidylinositol Phospholipases		 541(92)
9.1. Introduction
541(1)
9.2. PtdIns-nonspecific phospholipases
542(33)
9.2.1. Phospholipase A1
543(7)
9.2.1.1. Substrate specificity
544(3)
9.2.1.2. Methods of assay
547(3)
9.2.2. Phospholipase A2
550(11)
9.2.2.1. Substrate specificity
553(3)
9.2.2.2. Methods of assay
556(5)
9.2.3. Phospholipase C
561(7)
9.2.3.1. Substrate specificity
561(4)
9.2.3.2. Methods of assay
565(3)
9.2.4. Phospholipase D
568(7)
9.2.4.1. Substrate specificity
570(2)
9.2.4.2. Methods of assay
572(3)
9.3. PtdIns and GPtdlns-specific phospholipases
575(31)
9.3.1. Phospholipase A1 and A2
576(3)
9.3.1.1. Substrate specificity
577(1)
9.3.1.2. Methods of assay
577(2)
9.3.2. Phospholipase C
579(20)
9.3.2.1. Substrate specificity
582(9)
9.3.2.2. Methods of assay
591(8)
9.3.3. Phospholipase D
599(7)
9.3.3.1. Substrate specificity
603(1)
9.3.3.2. Methods of assay
604(2)
9.4. PtdIns(4,5)P2 activated phospholipases
606(20)
9.4.1. Phospholipase A2
606(3)
9.4.1.1. Affinity assay
607(1)
9.4.1.2. Catalytic assay
608(1)
9.4.2. Phospholipase C
609(3)
9.4.2.1. Affinity assays
609(2)
9.4.2.2. Catalytic assay
611(1)
9.4.3. Phospholipase D
612(14)
9.4.3.1. In vitro assay
619(5)
9.4.3.2. In vivo assay
624(2)
9.5. PtdIns(3,4,5)P3 activated phospholipases
626(7)
9.5.1. Phospholipase A2
626(1)
9.5.2. Phospholipase C
627(2)
9.5.3. Phospholipase D
629(4)
Chapter
10. Preparation of Standards		 633(56)
10.1. Introduction
633(1)
10.2. Phosphatidylinositol phosphates
634(19)
10.2.1. PtdIns monophosphates
635(10)
10.2.1.1. Ptdlns(4)P
635(4)
10.2.1.2. Ptdlns(3)P
639(5)
10.2.1.3. PtdIns(5)P
644(1)
10.2.2. PtdIns bis-phosphates
645(6)
10.2.2.1. PtdIns(4,5)P2
645(3)
10.2.2.2. Ptdlns(3,5)P2
648(1)
10.2.2.3. PtdIns(3,4)P2
649(2)
10.2.3. PtdIns trisphosphates
651(2)
10.2.3.1. PtdIns(3,4,5)P3
651(2)
10.3. Inositol phosphates
653(30)
10.3.1. Inositol monophosphates (InsP)
654(1)
10.3.1.1. Ins(1)P
654(1)
10.3.1.2. Ins(2)P
654(1)
10.3.1.3. Ins(3)P
655(1)
10.3.1.4. Ins(4)P
655(1)
10.3.1.5. Ins(5)P
655(1)
10.3.2. Ins bisphosphates
655(5)
10.3.2.1. Ins(1,2)P2
656(1)
10.3.2.2. Ins(1,3)P2 and Ins(3,4)P2
656(2)
10.3.2.3. Ins(1,4)P2
658(1)
10.3.2.4. Ins(1,5)P2
659(1)
10.3.2.5. Ins(3,5)P2
659(1)
10.3.2.6. Ins(4,5)-P2
659(1)
10.3.3. InsP3
660(8)
10.3.3.1. Ins(1,3,4)P3
660(2)
10.3.3.2. Ins(1,3,5)P3
662(1)
10.3.3.3. Ins(1,3,6)P3
662(1)
10.3.3.4. Ins(1,4,5)P3
662(4)
10.3.3.5. Ins(1,4,6)P3
666(1)
10.3.3.6. Ins(3,4,5)P3
666(1)
10.3.3.7. Ins(3,4,6)P3
666(1)
10.3.3.8. Ins(4,5,6)P3
667(1)
10.3.3.9. Ins(1,2cyc4,5)P3
667(1)
10.3.3.10. Ins(1,2,4)P3
667(1)
10.3.4. InsP4
668(8)
10.3.4.1. D/L [ 3H]-or [ 32P]Ins(1,2,3,4)P4
668(1)
10.3.4.2. Ins(1,2,4,5)P4
669(1)
10.3.4.3. Ins(1,3,4,5)P4
669(2)
10.3.4.4. Ins(1,3,4,6)P4
671(2)
10.3.4.5. Ins(1,4,5,6)P4
673(1)
10.3.4.6. Ins(3,4,5,6)P4
674(2)
10.3.5. InsP5s
676(6)
10.3.5.1. Ins(1,2,3,4,5)P5 and Ins(1,2,4,5,6)P5
679(1)
10.3.5.2. D-Ins(1,2,3,5,6)P5
680(1)
10.3.5.3. D-Ins(1,2,4,5,6)P5
681(1)
10.3.5.4. Ins(1,3,4,5,6)P5
681(1)
10.3.5.5. Ins(1,2,3,4,6)P5
682(1)
10.3.6. InsP6
682(1)
10.3.6.1. InsP6
682(1)
10.3.6.2. [ 3H]InsP6 and [ 32P]InsP6
683(1)
10.4. Inositol pyrosphosphates
683(2)
10.4.1. PP-InsP5
684(1)
10.4.2. PP-[ 3H]InsP4-PP
685(1)
10.5. Structural analogues
685(4)
10.5.1. Deoxy-myo-InsPs
685(1)
10.5.2. Membrane permeators
686(1)
10.5.3. Fluorescent derivatives
687(1)
10.5.4. Affinity reagents
688(1)
Chapter
11. InsPs and PtdInsPs as Signaling Molecules		 689(76)
11.1. Introduction
689(2)
11.2. InsPs as cellular signals
691(28)
11.2.1. Evidence for signaling
691(5)
11.2.1.1. Analytical
691(2)
11.2.1.2. Metabolic
693(2)
11.2.1.3. Molecular
695(1)
11.2.2. InsP-protein interaction
696(6)
11.2.2.1. Ins(1,4,5)P3 receptors
697(2)
11.2.2.2. Ins(1,3,4,5)P4 receptors
699(1)
11.2.2.3. Ins(3,4,5,6)P4 receptors
700(2)
11.2.2.4. InsP6 receptors
702(1)
11.2.3. Regulation of InsP kinases
702(9)
11.2.3.1. Ins(1,4,5)P31Ins(1,3,4,5)P4 cycle
703(2)
11.2.3.2. Ins(1,3,4,5,6)P5 /Ins(3,4,5,6)P4 cycle
705(2)
11.2.3.3. Ins(1,3,4,5,6)P5 /Ins(1,4,5,6)P4 cycle
707(1)
11.2.3.4. InsP6/InsP5 cycle
708(2)
11.2.3.5. Pyrophosphate cycle
710(1)
11.2.4. Specific biological effects
711(8)
11.2.4.1. Ion channel physiology
711(4)
11.2.4.2. Membrane dynamics
715(3)
11.2.4.3. Nuclear signaling
718(1)
11.3. PtdInsPs as cellular signals
719(6)
11.3.1. Evidence for signaling
720(5)
11.3.1.1. Analytical
720(2)
11.3.1.2. Metabolic
722(1)
11.3.1.3. Molecular
723(2)
11.3.2. PtdInsPs-protein interactions
725(9)
11.3.2.1. PtdInsP3 binding
726(3)
11.3.2.2. PtdInsP2 binding
729(3)
11.3.2.3. PtdInsP1 binding
732(2)
11.3.3. Regulation of PtdInsP kinases
734(6)
11.3.3.1. PtdIns 3-kinases
735(2)
11.3.3.2. PtdIns-4-kinases
737(1)
11.3.3.3. PtdIns 5-kinases
738(2)
11.3.4. Specific biological effects
740(25)
11.3.4.1. Membrane and vesicular trafficking
741(6)
11.3.4.2. Cell growth and differentiation
747(5)
11.3.4.3. Cytoskeletal organization and cell motility
752(4)
11.3.4.4. Apoptosis
756(6)
11.3.4.5. DNA synthesis
762(3)
References 765(186)
Index 951


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