Title: Integrins
Literature References: Family of transmembrane glycoproteins involved in cellular adhesion and signal transduction. Name derived from their ability to "integrate" activities of the extracellular matrix (ECM) and the cytoskeleton. Integrins exhibit widespread evolutionary distribution: identified in mammals and other vertebrates, insects, and yeast; homologues have been identified in plants. At least 20 have been identified in mammals; composed of ab heterodimers selected from among 16 a and 8 b subunits. The a subunits vary in size from 120-200 kDa with ~1000 amino acid residues and usually consist of a heavy and light chain joined by a disulfide bond; b subunits generally range from 90-120 kDa with ~800 amino acids. Three major subfamilies have been characterized. Most integrins bind to the Arg-Gly-Asp (RGD) amino acid sequence found on components of the ECM, such as fibronectin, q.v. Others bind to cell membrane proteins, such as the intercellular cell adhesion molecules (ICAMs), or to soluble ligands, such as fibrinogen, q.v. Several recognize more than one ligand. Integrins anchor cells to the ECM or to adjacent cells, regulate cell spreading and motility, and transduce extracellular stimuli into a variety of intracellular signals. Implicated in a variety of physiological processes including embryological development, wound healing, immune functions, thrombosis, and metastasis. Identification of membrane glycoproteins involved in cell adhesion: D. E. Wylie et al., J. Cell Biol. 80, 385 (1979). Identification of the transmembrane link between the ECM and the cytoskeleton: J. W. Tamkun et al., Cell 46, 271 (1986). Description of integrin family: R. O. Hynes, ibid. 48, 549 (1987); C. A. Buck, A. F. Horwitz, Annu. Rev. Cell Biol. 3, 179-205 (1987). Role of RGD sequence in cell adhesion: E. Ruoslahti, M. D. Pierschbacher, Science 238, 491 (1987). Review of integrin structure and ligand binding: A. Sonnenberg, Curr. Top. Microbiol. Immunol. 184, 7-35 (1993); D. S. Tuckwell, M. J. Humphries, Crit. Rev. Oncol. Hematol. 15, 149-171 (1993). Review of pharmacology: D. Cox et al., Med. Res. Rev. 14, 195-228 (1994). Review of role in signal transduction: A. Richardson, J. T. Parsons, BioEssays 17, 229-236 (1995); E. A. Clark, J. S. Brugge, Science 268, 233-239 (1995).
Derivative Type: b1-Integrins
Additional Names: VLA antigens; VLA integrins; very late activation antigens
Literature References: Widely distributed on various cell types. Share a common b1 chain complexed with various a chains. Bind to ECM components such as fibronectin, collagen, laminin. Ca2+/Mg2+-dependent. Review: L. G. M. Baldini, L. M. Cro, Leuk. Lymphoma 12, 197-203 (1994).
Derivative Type: b2-Integrins
Additional Names: Leukocyte integrins; Leu-Cam proteins; leukocyte adhesion molecules
Literature References: Contain the b2 chain; found on leukocytes. Bind to ICAMs, complement 3, and fibrinogen. Play an important role in regulating the immune system.
Derivative Type: b3-Integrins
Additional Names: Cytoadhesins
Literature References: Contain the b3 subunit; found on platelets, megakaryocytes and some melanoma cells. Ligands include fibrinogen, fibronectin, von Willebrand factor, vitronectin, and thrombospondin. Includes aIIbb3, also known as platelet glycoprotein IIb/IIIa (GPIIb-IIIa), a fibrinogen receptor involved in platelet aggregation. Review: M. H. Ginsberg et al., Thromb. Haemostasis 70, 87-93 (1993).

Others monographs:
Dicobalt OctacarbonylAmylocaine HydrochlorideAminophyllinePropanil
SethoxydimStibophenSulfuryl Fluoride2-Cyclohexyl-4,6-dinitrophenol
Potassium Tetracyanomercurate(II)AcenocoumarolPimozideAmylin
1-Ethyl-3-piperidinolInterleukin-1 Receptor Antagonistγ-OryzanolThomas Phosphate
©2016 DrugLead US FDA&EMEA