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Biology of phosphoinositides / edited by Shamshad Cockcroft. — Oxford ;New York : Oxford University Press, 2000.—(58.174234/B615b) |
Contents
Contents
List of contributors
Abbreviations
1 Regulation of phosphoinositide-specific phospholipase C isozymes 1
SUE GOO RHEE， BENOIT POULIN， SANG BONG LEE， AND FUJIO SEKIYA
1. Introduction 1
2. PLC isoforms and structural organization 2
3. Structure of PLC-81 and reaction mechanism of PLC 4
4. Activation of PLC-~/by receptor PTKs 7
5. Activation of PLC-~/by non-receptor PTKs in response to antigen receptors 10
6. Activation of PLC-~/by non-receptor PTKs in response to G-protein-coupled receptors 14
7. Activation of PLC-~ by other lipid-derived messengers 15
8. PLC-~/and mitogenic signaling 18
9. Activation of PLC-~ by Gc~q subunits 18
10. Activation of PLC-~ by G~3~/subunits 20
11. Targeted disruption of PLC-~ genes 21
12. Activation of PLC-8 isozymes 22
13. A requirement for phosphatidylinositol transfer protein in PLC signaling 22
References 22
2 Phosphoinositide 3-kinases: regulation by cell surface receptors and function of 3-phosphorylated lipids 32
LEN STEPHENS， ALEX MCGREGOR， AND PHILIP HAWKINS
1. Receptor-regulated phosphoinositide 3-kinases 32
2. Phosphoinositides 32
3. Types of PI3Ks 33
3.1 Type I PI3Ks 34
3.2 Type II PI3Ks 34
3.3 Type III PI3Ks 35
4. Metabolic relationships between 3-phosphorylated phosphoinositides 36
4.1 Ptdfns(3)P synthesis 36
4.2 PtdIns(3，5)P2 synthesis 37
4.3 PtdIns(3，4)P2 synthesis 37
4.4 Synthesis of PtdIns(3，4，5)P3 37
5. Metabolism of 3-phosphorylated phosphoinositides 38
5.1 PtdIns(3，4，5)Pg-directed phosphomonoesterases 38
5.2 PtdIns(3，4)P2 and Ptdlns(3)P directed phosphatases 39
6. Hormone-stimulated changes in 3-phosphorylated phosphoinositides 39
7. The protein kinase activity of PI3Ks 42
7.1 Mechanisms of regulation of type I PI3Ks 43
7.2 Autophosphorylation 43
7.3 Downstream of receptor-activated tyrosine kinases 43
7.4 PtdIns(3，4，5)P3 binding 45
7.5 Ceramide binding 45
7.6 Rho-family GTPases 45
7.7 SH3 domains and proline-rich motifs 46
7.8 Heterotrimeric G-protein 6~/subunits 47
7.9 Ras 48
8. Downstream signalling 49
8.1 What strategies? 49
8.2 The downstream targets 51
9. Type I PI3Ks in cell signalling pathways 57
9.1 Other PKB kinases 62
9.2 Targets of PKB 63
9.3 Other targets of PDK-1 64
10. Regulation of PKCs downstream of PDK-1 and type I PI3Ks 64
10.1 Conventional， or classical PKCs (a， [M， [~II， ?] 65
10.2 Novel and atypical PKCs (8， 0， e， lq， and ~， ~) 65
11. PDK-1 mediated phosphorylation of p70s6K 66
11.1 Type I PI3K-dependent phosphorylation of P70~K and PKC8 66
11.2 Additional potentially PI3K-dependent inputs to p70s6K 67
12. Type I PI3K-regulated Ca2+ entry 69
13. Type I PI3K-dependent activation of Rho family monomeric GTPases 71
14. Type I PI3K-dependent activation of p42 MAPK pathways 76
15. Type I PI3K-dependent regulation of RasGAPs 77
16. Integrin-mediated activation of type I PI3K-dependent signaling 78
17. Type I PI3K-dependent regulation of ARF-GEFs 81
18. Type I PI3Ks and ARF-GAPs 82
19. Type I PI3Ks and the cell cycle 83
19.1 Type I PI3K-dependent regulation of cell-cycle machinery 84
19.2 Type I PI3Ks and cell survival 86
20.Some cellular responses to receptor-activation involving PI3Ks 88
20.1 Receptor-activated superoxide formation 88
20.2 Chemotaxis 90
21. Conclusions 91
22 The future 92
22.1 The family of receptor-sensitive PI3Ks 92
22.2 3-Phosphorylated lipids as signals 92
References 93
3 Enzymes involved in the synthesis of PtdIns(4，5)P2 and
their regulation: PtdIns kinases and PtdInsP kinases 109
KIMBERLEY F. TOLIAS AND CHRISTOPHER L. CARPENTER
1. Introduction 109
2. Synthetic pathway 1: Ptdlns(4，5)P2 production via a PtdIns(4)P intermediate 111
2.1 Phosphatidylinositol 4-kinases 111
2.2 Phosphatidylinositol 4-phosphate 5-kinases 114
3. Synthetic pathway 2: PtdIns(4，5)P2 production via a PtdIns(5)P 118
intermediate 118
3.1 Enzymes that synthesize PtdIns(5)P 118
3.2 Phosphatidylinositol 5-phosphate 4-kinases 118
4. Cellular functions of Ptdlns(4，5)P2 120
4.1 Actin cytoskeleton 120
4.2 Vesicle trafficking 120
4.3 Other potential roles for PtdIns(4，5)P2 121
5. Conclusion 121
Acknowledgements 122
References 122
4 Pleckstrin homology domains: phosphoinositide-regulated membrane tethers 131
MARK A. LEMMON AND KATHRYN M. FERGUSON
1. Introduction 131
2. The structure of PH domains 133
2.1 Basic architecture 133
2.2 PH domains are electrostatically polarized 136
2.3 A disease-causing mutation functionally implicates one face of PH domains 136
3. PH domain ligands 137
3.1 PH domain distribution suggests a role in membrane association 137
3.2 The search for protein ligands for PH domains 137
3.3 PH domains bind to phosphoinositides 138
4. Membrane association of PH domains 143
4.1 Isolated PH domains can bind to cellular membranes 143
4.2 Signal-dependent membrane recruitment of PH domains by binding to PI 3-kinase products 143
5. Requirements for specific phosphoinositide recognition by PH domains 148
5.1 Structural considerations 148
5.2 Sequence predictors of high affinity phosphoinositide binding 150
6. Promiscuous phosphoinositide binding by many PH domains 152
7. Physiological relevance of promiscuous phosphoinositide binding by class II PH domains 153
7.1 Cooperation of PH domains with other targeting modules 153
7.2 Specific modulation of PH domain avidity as a mechanism for regulated membrane association 154
8. PH domains as intramolecular allosteric regulators 155
8.1 Kinases 155
8.2 Guanine nucleotide exchange factors for Rho-family GTPases 155
9. Conclusions 157
Acknowledgements 158
References 158
5 Regulation of cytoskeletal proteins by inositol lipids 166
LISA A. FLANAGAN AND PAUL A. JANMEY
1. Introduction 166
2. Classes of cytoskeletal proteins that bind polyphosphoinositides (PPIs) 166
2.1 Monomer-binding proteins and F-actin severing and capping proteins 166
2.2 Proteins that link actin to membrane adhesion complexes 168
2.3 Other F-actin-binding proteins 169
2.4 Other cytoskeletal proteins 170
3. Structures of Ptdlns(4，5)P2-binding sites in cytoskeletal proteins 170
4. Chemical specificity of the protein-lipid interaction 171
5. Effects of PPIs on actin assembly in vivo 171
5.1 Triggering actin assembly in cell extracts 171
5.2 Altering PtdIns(4，5)P2 levels in platelets and fibroblasts 172
5.3 Enhancing and blocking PPI synthesis in cells 173
6. Convergence of small GTPases and PPI signals to the cytoskeleton 174
7. Conclusions and unanswered questions 176
Acknowledgements 177
References 177
6 Physiological functions of phosphatidylinositol transfer proteinsMARCOS P. RIVAS， XINMIN LI， AND VYTAS A. BANKAITIS 183
1. Introduction183
2. Phospholipid transfer proteins: operational definitions 185
2.1 Lipid transfer assays 186
2.2 Categories of phospholipid transfer proteins 188
3. Phosphatidylinositol transfer proteins (PITPs) 189
3.1 Mammalian PITP function and neurodegeneration 190
3.2 Intracellular functions for mammalian PITP 191
3.3 Mammalian PITP activity: potential mode of regulation 194
4. Integral membrane PITPs: retinal degeneration in Drosophila 195
5. PITP function in the yeast secretory pathway 198
5.1 Sec14ps of dimorphic fungi 201
6. Higher plant PITPs and PITP-like molecules 202
7. Structural architecture of a PITP 204
8. Summary 205
Acknowledgements 205
References 205
7 Glycosylphosphatidylinositol-anchored proteins and their phospholipases 210
MARTIN G. LOW
1. Introduction 210
2. Distribution of GPI anchors 210
3. Structure of GPI anchors 213
3.1 The phosphatidylinositol group 213
3.2 The conserved glycan 213
3.3 Variable side-chains 214
4. Biosynthesis of GPI-anchored proteins 214
4.1 GPI biosynthesis 214
4.2 Attachment of GPI to proteins 217
4.3 Physiological consequences of GPI deficiency 219
5. Function of GPI anchors 220
5.1 GPI anchors provide stable binding to the cell surface 221
5.2 GPI anchors and lipid microdomains 222
5.3 GPI anchors and cell signaling 223
6. GPI-specific phospholipases 225
6.1 Bacterial phosphatidylinositol-specific phospholipase C 226
6.2 GPI-specific phospholipase C 228
6.3 GPI-specificphospholipaseD 230
References 231
8 Phosphatidylinositol 3-kinase and membrane trafficking 239
HARALD STENMARK
1. Introduction 239
2. PI 3-kinase and its lipid products 241
3. Experimental evidence for the involvement of PI 3-kinase in membrane trafficking 244
3.1 PI 3-kinase and membrane trafficking in yeast 245
3.2 PI 3-kinase and membrane trafficking in mammalian cells 245
4. Effectors of PI 3-kinase products in membrane trafficking 249
4.1 Effectors of PtdIns(3，4)P2 and PtdIns(3，4，5)P3 249
4.2 The C2 domain 251
4.3 Effectors of PtdIns(3)P 252
5. Conclusions and perspectives 258
Acknowledgements 260
References 260
9 Regulation of phospholipase D signalling by phosphoinositides 268
VICKI A. SCIORRA， MICHAEL A. FROHMAN， AND ANDREW J. MORRIS
1. Introduction 268
2. Structure and regulation of PLD 269
2.1 The superfamily of PLD enzymes: common structural features and catalytic mechanism 269
2.2 Complex regulation of PLD activity by GTP-binding proteins and protein kinases 273
2.3 Possible functions of PLD in cellular signalling and control of membrane transport 277
3. Direct and indirect regulation of PLD activity by phosphoinositides 281
3.1 Roles for phosphoinositides in regulation of PLD activity 282
3.2 Direct activation of PLD1 and PLD2 by phosphoinositides 282
3.3 Upstream roles for phosphoinositides in regulation of PLD activity 283
4. Concluding comments 287
Acknowledgements 288
References 288
10 Regulation of chloride channel conductance by Ins(3，4，5，6)P4; a phosphoinositide-initiated signalling pathway that acts downstream of Ins(1，4，5)P3 298
MELLISA W.Y.HO， MARK A.CAREW， XIAONIAN YANG， AND STEPHEN SHEARS
1. Introduction 298
2. Receptor-mediated regulation of Ins(3，4，5，6)P4 turnover 299
3. Identification of Ins(3，4，5，6)P4 as an inhibitor of C1- secretion 302
4. Ins(3，4，5，6)P4 inhibits Ca2+-activated C1- channels 304
5. Molecular and biophysical characterization of Ca2~-activated C1- channels 308
6. Specificity and cooperativity of Ins(3，4，5，6)P4 action 309
7. Mechanism of Ins(3，4，5，6)P4 action 310
8. Antagonizing Ins(3，4，5，6)P4: a potential therapy for cystic fibrosis? 313
9. Conclusions 313
References 314
11 Inositol phosphatases: constructive destruction of phosphoinositides and inositol phosphates 320
RUDIGER WOSCHOLSKI AND PETER J. PARKER
1. Introduction 320
2. 1-Phosphatases 322
3. 3-Phosphatases 324
4. 4-Phosphatases 325
5. Type 1 5-phosphatase 325
6. GAP-domain-containing phosphatases (GIPs) 326
7. SHIPs 327
8. SCIPs 328
9. Inositol phosphatases and membrane trafficking 329
10. Inositol phosphatases and cell signaling 330
References 331
Index 339
