Receptor superfamilies mechanism

Both receptor types are members of the NGF receptor superfamily and exhibit the characteristic four (cysteine-rich) repeat units in their extracellular domain. The extracellular domains of TNF-R55 and TNF-R75 exhibit only 28 per cent homology and their intracellular domains are devoid of any homology, indicating the likely existence of distinct signalling mechanisms. 

The EPO receptor is a member of the haemopoietic cytokine receptor superfamily. Its intracellular domain displays no known catalytic activity, but it appears to couple directly to the JAK2 kinase (Chapter 8) that likely promotes the early events of EPO signal transduction. Other studies have implicated additional possible signalling mechanisms, including the involvement of G proteins, protein kinase C and Ca2+. The exact molecular events underlining EPO signal transduction remain to be elucidated in detail. 

In the sympathetic part of the peripheral autonomic nervous system the simation is less complicated since only the sympathetically innervated visceral organs have receptors sensitive to the transmitter of the postganglionic sympathetic neuron noradrenaline. However, the noradrenaline sensitive receptors, which all belong to the G-protein coupled receptor superfamily, can be subdivided in at least three subtypes ai-, a - and jSi-adrenoceptors. These receptors are to a similar extent sensitive to adrenaline, a humoral transmitter which is released under sympathetic control from the adrenal medulla. Adrenaline, in contrast to noradrenaline has affinity to a forth type, the /32-adrenoceptor. In general drug interacting with the autonomous nervous system can be subdivided according to their mechanism of action. 

Kavelaars A, Jeurissen F, von Frijtag Drabbe Kunzel J, Herman van Roijen J, Rijkers GT, Heijnen CJ (1993) Substance P induces a rise in intracellular calcium concentration in human T lymphocytes in vitro evidence of a receptor-independent mechanism. J Neuroimmunol 42 61-70 Kemppainen RJ, Behrend EN (1998) Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. J Biol Chem 273 3129-3131... 

Figure 19.2. Schematic representation of some receptor superfamilies. This figure represents the common mechanisms of the four major receptor families discussed in Section 19.2. Example 1 is of the G protein-coupled receptor. Example 2 represents the ionotropic receptor (ligand-gated ion channel) superfamily, on which multiple binding sites are known to exist (see Figure 19.1). Example 3 represents the steroid receptor superfamily. Example 4 depicts the enzyme-linked receptor superfamily.

Ming-Jer Tsai and B. W. O Malley. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem, 63, 451-486, 1994. 

Secretion of ecdysone starts the many biochemical processes that are necessary for the molting. The cells in the epidermis are stimulated to produce a new cuticle, and when ready, the insect will creep out of its old skin. The molecular mechanism of ecdysone has been studied in some detail. The molecular target of ecdysone and other ecdysteroids consists of at least two proteins, the ecdysteroid receptor (EcR) and ultraspiracle (USP). Both EcR and USP are members of the steroid hormone receptor superfamily with characteristic ligand-binding domains. An EcR-USP-ecdysteroid complex is formed, which activates several genes that code for transcription factors, i.e., proteins that activate or repress the activity of other genes, and the appropriate amounts of proteases and other enzymes necessary to degrade old structures and rebuild new ones are formed in a time-controlled sequence. 

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