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Vol. 50, Issue 2, 197-264, June 1998
Department of Pharmacology, School of Medicine, University of North
Carolina, Chapel Hill, North Carolina
I. Introduction
II. Families of Cell Adhesion Receptors
A. Overview
B. Integrins
C. Cadherins
D. Immunoglobulin-Cell Adhesion Molecule Superfamily
E. Selectins
III. The Components of Adhesive Junctions
A. Integrin Containing Focal Contacts
1. Cytoskeletal proteins
2. Transmembrane proteins: tetraspanners, integrin-associated
protein 50, caveolin
3. Cytoplasmic integrin-binding proteins
4. Interactions with Integrin Heterodimers.
B. Other Adhesive Junctions
1. Cadherin-mediated adherence junctions
2. Junctions containing ezrin/radixin/moesin proteins
IV. Direct Signal Transduction by Integrins: Activation of Tyrosine
Kinases
A. Introduction
B. Focal Adhesion Kinase-Mediated Events
1. Linkage to integrin signaling
2. Mechanism of activation
3. The role of Src in focal adhesion kinase signaling
4. Other focal adhesion kinase-binding proteins
5. Inhibition of focal adhesion kinase activity
6. Focal adhesion kinase substrates
7. Focal adhesion kinase function
8. Focal adhesion kinase summary
C. Focal Adhesion Kinase Family Members
D. Src Family Members
1. Activation of Src family members downstream of 
1 integrins
2. Activation of Src family members downstream of 2 integrins
E. Other Tyrosine Kinases Activated by Integrins
1. C-Abl
2. Spleen tyrosine kinase
F. Summary
V. Direct Signal Transduction by Integrins: Activation of the
Mitogen-Activated Protein Kinase Cascade
A. Experimental Approaches and Cell Types
B. Time Course of Integrin-Mediated Mitogen-Activated Protein
Kinase Activation and Its Consequences
C. Mechanisms for Integrin-Mediated Mitogen-Activated Protein
Kinase Activation
1. Mechanism of growth factor activation of mitogen-activated
protein kinase
2. Mechanism of integrin-mediated activation of mitogen-activated
protein kinase
3. The role of focal contact hierarchies and cytoskeletal
organization in integrin-mediated mitogen-activated protein kinase
activation
D. Integrin-Mediated Activation of the Jun N-Terminal
Kinase/Stress-Activated Protein Kinase Pathway
E. Functions of Integrin-Mediated Mitogen-Activated Protein Kinase
Activation
1. Transcriptional regulation
2. Cytoplasmic targets
3. Cell adhesion and motility
F. Summary
VI. Integrins and Rho Family Guanosine 5'-Triphosphatases
A. Introduction
B. Regulation of Activity
C. Proteins that Interact with Rho Family Guanosine
5'-Triphosphatases
D. Rho Guanosine 5'-Triphosphatases, Cell Cycle
Progression, and Transcriptional Regulation
E. Rho Guanosine 5'-Triphosphatases and the Cytoskeleton
1. Lipid metabolism
2. Rho, mitogen-activated protein kinase, and contractility
F. Summary
VII. Other Aspects of Integrin Signaling
A. Signaling by Specific Integrins
B. Cross-Talk Between Integrins
C. Mechanochemical Aspects of Adhesion Signaling
D. Relationships Between Integrin Signaling Pathways
VIII. Signaling by Cadherins, Selectins, and Immunoglobulin-Cell
Adhesion Molecules
A. Cadherin Signaling
1. Cadherins, catenins, adenomatous polyposis coli, and the Wnt
pathway
2. Components of the Wnt-cadherin signaling pathway
3. A model for the Wnt-cadherin signaling pathway
4. Other aspects of cadherin signaling
B. Signaling by Immunoglobulin-Cell Adhesion Molecules
1. Neural immunoglobulin-cell adhesion molecules
2. Other signaling by immunoglobulin-cell adhesion molecules
C. Signaling by Selectins
D. Collagen Binding Receptor Tyrosine Kinases
E. Summary
IX. Adhesion Modulation of Signaling by Soluble Mitogens and
Differentiation Factors
A. Introduction
B. Integrin Modulation of Growth Factor Signaling
C. Signal Modulation by Other Cell Adhesion Molecules
1. Neuronal cell adhesion molecules
2. Cadherin-catenin complexes
3. Selectins
D. Summary
X. Cell Adhesion Receptors and the Control of Cell Cycle and
Programmed Cell Death
A. Cell Adhesion and Cell Cycle Control
1. Overview of the cell cycle machinery
2. Links between signaling pathways and the cell cycle
3. Cell cycle activities regulated by cell adhesion
4. Anchorage regulation of the cell cycle: a role for specific
integrins?
B. Cell Adhesion and Apoptosis
1. Overview of apoptosis
2. Anchorage regulation of apoptosis
XI. Cell Adhesion Receptors and the Regulation of Gene Expression
XII. Conclusions
Acknowledgments
References
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 W.-Y. Lui, D. D. Mruk, W. M. Lee, and C. Y. Cheng Adherens Junction Dynamics in the Testis and Spermatogenesis J Androl, January 1, 2003; 24(1): 1 - 14. [Full Text] [PDF]
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 I. Verbovetski, H. Bychkov, U. Trahtemberg, I. Shapira, M. Hareuveni, O. Ben-Tal, I. Kutikov, O. Gill, and D. Mevorach Opsonization of Apoptotic Cells by Autologous iC3b Facilitates Clearance by Immature Dendritic Cells, Down-regulates DR and CD86, and Up-regulates CC Chemokine Receptor 7 J. Exp. Med., December 16, 2002; 196(12): 1553 - 1561. [Abstract] [Full Text] [PDF]
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K. L. Wingerd, N. L. Goodman, J. W. Tresser, M. M. Smail, S. T. Leu, S. J. Rohan, J. L. Pring, D. Y. Jackson, and D. O. Clegg alpha 4 Integrins and Vascular Cell Adhesion Molecule-1 Play a Role in Sympathetic Innervation of the Heart J. Neurosci., December 15, 2002; 22(24): 10772 - 10780. [Abstract] [Full Text] [PDF]
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P. A. Pennisi, V. Barr, N. P. Nunez, B. Stannard, and D. Le Roith Reduced Expression of Insulin-like Growth Factor I Receptors in MCF-7 Breast Cancer Cells Leads to a More Metastatic Phenotype Cancer Res., November 15, 2002; 62(22): 6529 - 6537. [Abstract] [Full Text] [PDF]
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 C. Heneweer, L. H. Kruse, F. Kindhauser, M. Schmidt, K. H. Jakobs, H.-W. Denker, and M. Thie Adhesiveness of human uterine epithelial RL95-2 cells to trophoblast: Rho protein regulation Mol. Hum. Reprod., November 1, 2002; 8(11): 1014 - 1022. [Abstract] [Full Text] [PDF]
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 E. Geimonen, S. Neff, T. Raymond, S. S. Kocer, I. N. Gavrilovskaya, and E. R. Mackow Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses PNAS, October 15, 2002; 99(21): 13837 - 13842. [Abstract] [Full Text] [PDF]
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C. Y. Cheng and D. D. Mruk Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development Physiol Rev, October 1, 2002; 82(4): 825 - 874. [Abstract] [Full Text] [PDF]
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 J. Gingras, S. Rassadi, E. Cooper, and M. Ferns Agrin plays an organizing role in the formation of sympathetic synapses J. Cell Biol., September 16, 2002; 158(6): 1109 - 1118. [Abstract] [Full Text] [PDF]
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A. C. Semel, E. C. Seales, A. Singhal, E. A. Eklund, K. J. Colley, and S. L. Bellis Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors J. Biol. Chem., August 30, 2002; 277(36): 32830 - 32836. [Abstract] [Full Text] [PDF]
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Q.-H. Sun, C.-Y. Liu, R. Wang, C. Paddock, and P. J. Newman Disruption of the long-range GPIIIa Cys5-Cys435 disulfide bond results in the production of constitutively active GPIIb-IIIa (alpha IIbbeta 3) integrin complexes Blood, August 28, 2002; 100(6): 2094 - 2101. [Abstract] [Full Text] [PDF]
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M. M. Monick, L. Powers, N. Butler, T. Yarovinsky, and G. W. Hunninghake Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L390 - L402. [Abstract] [Full Text] [PDF]
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S. S. Smyth and C. Patterson Tiny dancers: the integrin-growth factor nexus in angiogenic signaling J. Cell Biol., July 8, 2002; 158(1): 17 - 21. [Abstract] [Full Text] [PDF]
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K. Ikeda, L.-H. Wang, R. Torres, H. Zhao, E. Olaso, F. J. Eng, P. Labrador, R. Klein, D. Lovett, G. D. Yancopoulos, et al. Discoidin Domain Receptor 2 Interacts with Src and Shc following Its Activation by Type I Collagen J. Biol. Chem., May 17, 2002; 277(21): 19206 - 19212. [Abstract] [Full Text] [PDF]
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 C. A. Pettersen and K. B. Adler Airways Inflammation and COPD* : Epithelial-Neutrophil Interactions Chest, May 1, 2002; 121(5_suppl): 142S - 150S. [Abstract] [Full Text] [PDF]
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A. Obergfell, K. Eto, A. Mocsai, C. Buensuceso, S. L. Moores, J. S. Brugge, C. A. Lowell, and S. J. Shattil Coordinate interactions of Csk, Src, and Syk kinases with {alpha}IIb{beta}3 initiate integrin signaling to the cytoskeleton J. Cell Biol., April 15, 2002; 157(2): 265 - 275. [Abstract] [Full Text] [PDF]
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W. C. Wildering, P. M. Hermann, and A. G. M. Bulloch Rapid Neuromodulatory Actions of Integrin Ligands J. Neurosci., April 1, 2002; 22(7): 2419 - 2426. [Abstract] [Full Text] [PDF]
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B. P. Eliceiri, X. S. Puente, J. D. Hood, D. G. Stupack, D. D. Schlaepfer, X. Z. Huang, D. Sheppard, and D. A. Cheresh Src-mediated coupling of focal adhesion kinase to integrin {alpha}v{beta}5 in vascular endothelial growth factor signaling J. Cell Biol., April 1, 2002; 157(1): 149 - 160. [Abstract] [Full Text] [PDF]
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W.-M. Yu, T. S. Hawley, R. G. Hawley, and C.-K. Qu Role of the docking protein Gab2 in beta 1-integrin signaling pathway-mediated hematopoietic cell adhesion and migration Blood, April 1, 2002; 99(7): 2351 - 2359. [Abstract] [Full Text] [PDF]
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J. Yi, S. Kloeker, C. C. Jensen, S. Bockholt, H. Honda, H. Hirai, and M. C. Beckerle Members of the Zyxin Family of LIM Proteins Interact with Members of the p130Cas Family of Signal Transducers J. Biol. Chem., March 8, 2002; 277(11): 9580 - 9589. [Abstract] [Full Text] [PDF]
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 P. Stawowy, F. Blaschke, P. Pfautsch, S. Goetze, F. Lippek, B. Wollert-Wulf, E. Fleck, and K. Graf Increased myocardial expression of osteopontin in patients with advanced heart failure Eur J Heart Fail, March 1, 2002; 4(2): 139 - 146. [Abstract] [Full Text] [PDF]
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S. Y. Cho and R. L. Klemke Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold J. Cell Biol., February 18, 2002; 156(4): 725 - 736. [Abstract] [Full Text] [PDF]
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 J.D. HOOD and D.A. CHERESH Targeted Delivery of Mutant Raf Kinase to Neovessels Causes Tumor Regression Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 285 - 292. [Abstract] [PDF]
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B. P. Eliceiri Integrin and Growth Factor Receptor Crosstalk Circ. Res., December 7, 2001; 89(12): 1104 - 1110. [Abstract] [Full Text] [PDF]
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A. M. Freyer, S. R. Johnson, and I. P. Hall Effects of Growth Factors and Extracellular Matrix on Survival of Human Airway Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 569 - 576. [Abstract] [Full Text] [PDF]
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N. K. Kaba and P. A. Knauf Hypotonicity induces L-selectin shedding in human neutrophils Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1403 - C1407. [Abstract] [Full Text] [PDF]
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K. M. Giles, K. Ross, A. G. Rossi, N. A. Hotchin, C. Haslett, and I. Dransfield Glucocorticoid Augmentation of Macrophage Capacity for Phagocytosis of Apoptotic Cells Is Associated with Reduced p130Cas Expression, Loss of Paxillin/pyk2 Phosphorylation, and High Levels of Active Rac J. Immunol., July 15, 2001; 167(2): 976 - 986. [Abstract] [Full Text] [PDF]
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E. Chamoux, L. Bolduc, J.-G. Lehoux, and N. Gallo-Payet Identification of Extracellular Matrix Components and Their Integrin Receptors in the Human Fetal Adrenal Gland J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2090 - 2098. [Abstract] [Full Text]
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M. Balzar, I. H. Briaire-de Bruijn, H. A. M. Rees-Bakker, F. A. Prins, W. Helfrich, L. de Leij, G. Riethmüller, S. Alberti, S. O. Warnaar, G. J. Fleuren, et al. Epidermal Growth Factor-Like Repeats Mediate Lateral and Reciprocal Interactions of Ep-CAM Molecules in Homophilic Adhesions Mol. Cell. Biol., April 1, 2001; 21(7): 2570 - 2580. [Abstract] [Full Text]
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 M. Edlund, T. Miyamoto, R. A. Sikes, R. Ogle, G. W. Laurie, M. C. Farach-Carson, C. A. Otey, H. E. Zhau, and L. W. K. Chung Integrin Expression and Usage by Prostate Cancer Cell Lines on Laminin Substrata Cell Growth Differ., February 1, 2001; 12(2): 99 - 107. [Abstract] [Full Text]
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 M. TICCHIONI, V. RAIMONDI, L. LAMY, J. WIJDENES, F. P. LINDBERG, E. J. BROWN, and A. BERNARD Integrin-associated protein (CD47/IAP) contributes to T cell arrest on inflammatory vascular endothelium under flow FASEB J, February 1, 2001; 15(2): 341 - 350. [Abstract] [Full Text] [PDF]
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A. K. Scaffidi, Y. P. Moodley, M. Weichselbaum, P. J. Thompson, and D. A. Knight Regulation of human lung fibroblast phenotype and function by vitronectin and vitronectin integrins J. Cell Sci., January 10, 2001; 114(19): 3507 - 3516. [Abstract] [Full Text] [PDF]
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M Reyes-Reyes, N Mora, A Zentella, and C Rosales Phosphatidylinositol 3-kinase mediates integrin-dependent NF-(&kgr;)B and MAPK activation through separate signaling pathways J. Cell Sci., January 4, 2001; 114(8): 1579 - 1589. [Abstract] [PDF]
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 B. Steffensen, L. Hakkinen, and H. Larjava Proteolytic Events of Wound-Healing -- Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules Critical Reviews in Oral Biology & Medicine, January 1, 2001; 12(5): 373 - 398. [Abstract] [Full Text] [PDF]
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C. B. Jones, J. McIntosh, H. Huang, A. Graytock, and D. G. Hoyt Regulation of Bleomycin-Induced DNA Breakage and Chromatin Structure in Lung Endothelial Cells by Integrins and Poly(ADP-Ribose) Polymerase Mol. Pharmacol., January 1, 2001; 59(1): 69 - 75. [Abstract] [Full Text]
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S. K. Alahari, J. W. Lee, and R. L. Juliano Nischarin, a Novel Protein That Interacts with the Integrin {alpha}5 Subunit and Inhibits Cell Migration J. Cell Biol., December 4, 2000; 151(6): 1141 - 1154. [Abstract] [Full Text] [PDF]
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