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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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