Tyrosine kinase-linked receptors

Figure 4.20 Tyrosine kinase-linked receptors (a) those with inherentTK activity insulin receptor. The intracellular tail and cytoplasmic proteins become phosphoryLated following hormone engagement with the ligand-binding domain...

Molecules that prevent a response from receptors are called antagonists. Sometimes antagonists for tyrosine kinase-linked receptors are called inhibitors. Why is this appropriate ... 

Chemotherapy agents, such as DNA alkylators (see Chapter 6), have traditionally been administered intravenously because of their high chemical reactivity and low bioavailability. During the past decade, a new class of oral anticancer drug, the tyrosine kinase inhibitors, has been developed. These inhibitors bind membrane-bound tyrosine kinase-linked receptors (TKLR) (see Chapter 5). 

Furthermore, recent researches have shown that there is another type of metabolic pathway of inositol phospholipids where the tyrosine kinase-linked receptors embedded in the cell membrane... 

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... 

Kinase-linked receptors are. surface receptors thal possess (usually) intrinsic tyrosine kiiutse activity. They include receptors for insulin. cytokiiie.s and growth factors (Chapter 36). 

Tyrosine kinase receptors are important enzyme-linked receptors... 

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. 

PKA and PKC are, however, not the only kinases to regulate TRPVl. The Ca /calmodulin-dependent kinase II (CaMKII) sensitizes TRPVl by phosphorylation [57, 58], as does phophatidylinositol 3-kinase (PI3K) via its downstream target AKT [59]. This latter finding links TRPVl to the ERK (extracellular signal-regulated protein kinase) pathway. The non-receptor tyrosine kinase Src likewise potentiates capsaicin-induced currents [60]. 

RECEPTORS CONTAINING PROTEIN TYROSINE KINASES 8.2.1 Cross-Linking of Receptors Causes Activation... 

Dimerization allows the kinase activity of both intracellular chains to encounter target sequences on the other, linked receptor molecule. This enables the intermolecular cross-phosphorylation of several tyrosine residues (Figure 8.2). The phosphorylated dimer then constitutes the active receptor. It possesses an array of phosphotyrosines that enable it to bind proteins to form receptor signaling complexes. Additionally, the dimerized and phosphorylated receptor has the potential of phospho-rylating its targets. 

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. 

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