Classes tyrosine kinase receptors

The insulin receptor is a transmembrane receptor belonging to the tyrosine kinase receptor class (Figure 13.6). Two a and two /S subunits make up the insulin receptor. The p subunits pass through the cell membrane and are linked by disulphide bonds. The a and p subunits are encoded by a single gene (INSR). 

Pharmacodynamic (PD) biomarkers are markers of a certain pharmacological response, which are of special interest in dose optimization studies. Pharmacodynamic modeling is often based on animal studies and known behavior of certain individual drug classes. The models are used to support initial dosing studies. Two examples include cyclooxygenase inhibitors and a new tyrosine kinase receptor inhibitor [35-38]. 

The majority of receptors affecting acid secretion belong to the G7 (seven transmembrane segments) class of receptors (H2, muscarinic, CCK2, somatostatin, prostaglandin). The EGF/TGF-a receptor, which also inhibits acid secretion, is a tyrosine kinase receptor (single transmembrane segment with an intracellular ATP kinase domain). 

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

Activation of Mi, M3, and M5 mAChRs does not only lead to the generation of IP3 followed by the mobilization of intracellular Ca2+, but also results in the stimulation of phospholipase A2, phospholipase D, and various tyrosine kinases. Similarly, M2 and M4 receptor activation does not only mediate the inhibition of adenylyl cyclase, but also induces other biochemical responses including augmentation of phospholipase A2 activity. Moreover, the stimulation of different mAChR subtypes is also linked to the activation of different classes of mitogen-activated protein kinases (MAP kinases), resulting in specific effects on gene expression and cell growth or differentiation. 

The catalytic pi 10 subunit has four isoforms, all of which contain a kinase domain and a Ras interaction site. In addition, the a, (3, and y isoforms possess an interaction site for the p85 subunit. The class I enzymes can be further subdivided class IA enzymes interact through their SH2 domains with phosphotyrosines present on either protein tyrosine kinases or to docking proteins such as insulin-receptor substrates (IRSs GAB-1) or linkers for activation of T cells (LATs in the case of T cells). 

The neurotrophins interact with two distinct cell surface receptor species [5,6,9] (Fig. 27-2). The neurotrophins bind to the Trk family of receptors, which serve as the principal signal transducer for this class of growth factors. The Trk receptors comprise a small, highly related family of molecules that possess an extracellular ligand binding domain that selectively interacts with the individual neurotrophin species. Trk A specifically binds NGF, TrkB interacts with BDNF and NT4/5, and TrkC preferentially binds NT3. Importantly, the Trk receptors have an intracellular tyrosine kinase domain that is activated upon neurotrophin binding. The kinase domains of the Trk family members are highly conserved and the Trks differ mainly in the structure of their extracellular domains. Trk receptor expression is limited to neurons and the... 

One important class of these systems is the membrane embedded enzyme-receptors such as tyrosine kinases. The binding of the extracelullar agonists... 

We discuss later a number of receptor classes and analyze how signals are transduced. These receptors are G-protein coupled receptors (GPCRs), ion channel receptors, tyrosine kinases, and intracellular receptors. A list of selected... 

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