Integrins
Integrins are a large family of homologous transmembrane linker proteins that include collagen, fibronectin and laminin. They are a family of cell-surface proteins that mediated cell adhesion, a process that is essential for anchorage, and act as cues for cell migration and signals for growth and differentaition.1 In addition to their biological importance to fundamental cellular processes, integrins play a part in immune function, tissue repair, tumour invasion, and platelet aggregation.2 The integrins are a major family of adhesion receptors produced by most cell types and are a means by which the cell senses its immediate environment and responds to changes in extracellular matrix composition. dynamic family of receptors capable of translating information into and out of the cell.3 Each member of the integrin family consists of a non-covalently linked heterodimer of an a chain and a b chain, which are transmembrane proteins with short cytoplasmic tails. They are subdivided! according to the eight different b subunits, and more than 20 different ab combinations have been recognised. Different types of cells assemble and express different b complexes. Although most cells express diverse integrins, some are found
in b1 teratomas range from increased apoptosis to abnormal deposition of ECM proteins and a defect in angiogenesis. An increase in cell death may result from the fact that teratomas are composed of normal cells which still need anchorage for survival. It is known that normal cells will undergo apoptosis when deprived of their interaction with the surrounding matrix The molecular mechanism of integrin-mediated cell survival is still poorly understood. Certain integrins can induce bcl-2 expression which is a well known suppressor of apotosis. Other integrins activate via Shc the MAP kinase pathway, Since inhibition of MAP kinase can induce apoptosis integrin mediated elevation of MAP kinase activity conceivably could promote cell survival. An important aspect of the involvement of b1 integrin in angiogenesis is the potential implication for tumor treatment. Tumors depend largely on effective angiogenesis. Several proteins have been identified in the past which block tumor angiog! Integrins differ from other cell-surface receptors in that they bind their ligands with a low affinity (10^6-10^9 liters/mole) and that they are usually present at 10-100 fold higher concentration on the cell surface. The integrins however can only bind their ligands when they exceed a certain minimal number of integrins at certain places, called focal contacts and hemidesmosomes. So when the integrins are diffusely distributed over the cell surface, no adhesion will be present, but when after a certain stimuli these integrins cluster for example in focal contacts their combined weak affinities give rise to a spot on the cell surface which has enough adhesive (sticking) capacity to adhere to the extracellular matrix. This is a very usefull situation, because in this way cells can bind simultaniously but weakly to large numbers of matrix molecules and still have the uppertunity to explore their environment without losing all attachment to it by building or breaking down focal c! 11. Alon R., Kassner P., Carr M., Finger E.B., Hemler M.A., Springer T.A. Lymphocyte VLA-4 can mediate cell tethering, rolling and firm adhesions on VCAM-1 under flow. Cell. Biology. 128, 1243-1253. (1995) Conclusion: Integrins - holding it together! only on specific cell types. Eg. The aIIbb3 integrin is found exclusively on megakaryocytes and platelets, and the b2 (CD18) integrin is detected only on leucocytes. Many integrins bind to extracellular-matrix proteins (fibronectin, various collagens, von Willebrand factor, and vitronectin) and take part in the mediation of interactions between cells and the extracellular matrix; other integrins bind to cell-membrane proteins (eg, intracellular adhesion molecules 1 and 2) and mediate cell-cell adhesion. Integrins also function a cell signal transducers, activating various intracellular signalling pathways when activated by matrix binding. A cell can regulate the activity of its integrins by altering either their matrix-binding site or thei! 4. Wolf S. Structure of integrins. Protein science, 30, 190-200 (1997). Tumorigenis: A number of reports have demon-strated that integrins influence tumorigenicity ranging from local tumor growth to metastasis10. On the other hand, however, it has become clear with other animal model studies that tumori-genicity is not regulated by 'specific tumor integrin(s)'. These studies link tumori-genicity to a reduced expression of b1 integrin and others to an elevated expression. In addition, tumor c
Some common words found in the essay are:
RNA's Integrins, Introduction Integrins, Leukocytes White, Conclusion Integrins, Background Integrin, ECM Hence, Life Fertilisation, Shc MAP, Filaments Integrins, GS Characterization, extracellular matrix, actin filaments, b1 integrin, adhesion receptors, amino acids, intracellular signalling, cell adhesion, matrix binding, adhesion molecules, blood cells, intracellular signalling pathways, yes actin filaments, signalling pathways activated, pathways activated matrix, activated matrix binding,
Approximate Word count = 2332
Approximate Pages = 9 (250 words per page double spaced)
|
