Receptors intrinsic enzyme activity

Ligand-gated ion channels G protein-coupled receptors Receptors with intrinsic enzyme activity INTRODUCTION... 

B Receptors with intrinsic enzyme activity C Receptors linked to cytosoiic tyrosine-kinases... 

FIGURE 8.3 Domain organization of proteins that associate with phosphorylated tyrosine kinase (PTK)-containing receptors. Proteins that associate with tyrosine-phosphorylated receptors contain SH2 or PTB domains, which recognize specific amino-acid stretches in the vicinity of phosphorylated tyrosine residues. Unlike the enzymes, the adaptors lack intrinsic catalytic activity but serve to link phosphorylated receptors with other effector proteins. Some of the proteins presented in this figure are discussed in this chapter. 

Bioactive chemicals such as pesticides, disinfectants, and pharmaceuticals must have certain reactivity within their range of application. They exert their reactivity within a special environment, such as within the human body, where they are activated in a specific manner. It should also be noted that some pharmaceuticals are applied as prodrugs. Before they can exert their desired effects, prodrugs are activated in the human body. Any effect, wanted or unwanted, is based on interaction of APIs with other molecules, for example, receptors or enzymes. They display their reactivity within a specific environment, such as within the human body, where they are activated in a specific manner. In summary, fully stable chemicals and pharmaceuticals would not be of any use in most cases, because they would not undergo any interaction or reaction with the environment, which is often required for their application. We normally speak of the stability of a chemical without mentioning the context of its environment. We assume that the stability of a chemical is an intrinsic... 

The EGF receptor possesses intrinsic kinase activity and will transfer the terminal phosphate of ATP specifically to the parahydroxyl group of tyrosine residues in certain substrate proteins. The region that encodes this enzyme activity lies between residues 690 and 940 of the cytoplasmic domain (Fig. 1). These sequences are the central, common structural feature shared by the GFRs which possess ligand-stimulated tyrosine kinase activity. Towards the N-terminal end of this region are residues involved in binding the substrate ATP, but it is not known which residues interact with substrate proteins. This is the only known activity of the EGF... 

Fig. 6-22 Cycle of activation and deactivation of heterotrimeric G-proteins. The ligand-bound receptor acts as a guanine nucleotide-exchange factor that replaces GDP with GTP on the a subunit. The a-GTP and /3-y-GTP subunits then separate to activate downstream target enzymes. The cycle is completed by the action of intrinsic GTPase activity in the a subunit. Free a-GDP subunits readily reassociate with free fiy subunits to form inactive apy heterotrimers. G-protein activation represents a site of amplification in signaling pathways for every ligand bound receptor molecule in the membrane, it is estimated that hundreds or thousands of G-protein molecules are activated.

Enzyme receptors are transmembrane receptors with intrinsic enzymatic activity. Examples are the receptor tyrosine kinases (RTKs), which autophosphorylate their own tyrosine residues, such as the growth factor receptors and the insulin receptor. And, finally, there are the intracellular DNA sinding receptors. They bind lipophilic ligands that pass through the membrane. They address genes directly. Examples are the steroid hormone receptors (see Chapter 11). (This figure was donated by Professor Martin Lohse, University of Wurzburg.)... 

Receptors of mediators inclnding an intrinsic ion channels (ligand-gated ion channels snch as nicotinic receptors), or an enzyme activity (i.e. a tyrosine kinase activity such as insnlin receptors, or ganylyl cyclase activity such as ANF receptors) have ligands for their receptor part (agonists and antagonists) as well as for their ion channel (openers and inhibitors or blockers) or enzyme part (inhibitors). 

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