Protein tyrosine kinase PTK

More recently, MAPKs such as ERK,51 54 BMK-1,55 p3843,51 and JNK56,57 have been implicated in the regulation of Cx43 phosphorylation. BMK-1 phosphorylates the serine residue 255 of Cx43,55 while other MAPKs contribute to Cx43 phosphorylation of the serine residues 279 and 282.54,58,59 Increased phosphorylation of Cx43 by MAPKs increases electrical conductance of paired rat cardiomyocytes.51 

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Protein tyrosine kinases (PTKs) are enzymes (EC 2.7.1.112) that catalyze the transfer of the y-phosphate group of ATP to tyrosine residues of protein substrates. The activity of PTKs is controlled in a complex manner by posttranslational modifications and by inter- and intramolecular complex formations. 

In B lymphocytes, coupling of the antigen receptors to Erk MAPkinase is protein tyrosine kinase (PTK)-dependent (Pao et al, 1997). Following ligation of the BCR (Fig. 19.2) the PTK, Lyn, tyrosine phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) on the accessory transducing molecules Ig-a and Ig-(3, leading to the recruitment... 

Cytokine receptors can be divided into two groups those whose intracellular domains exhibit intrinsic protein tyrosine kinase (PTK) activity and those whose intracellular domains are devoid of such activity. Many of the latter group of receptors, however, activate intracellular soluble PTKs upon ligand binding. 

A further consideration is that receptors which primarily activate one pathway may, on occasion, activate a second pathway (Fig. 10-10). An example is the ability of GPCRs, such as a2-adrenergic receptors or mAChRs, to activate the MAPK cascade. Activation of adenylyl cyclase-linked receptors results in the release of G protein Py subunits, which, probably via an intermediary protein tyrosine kinase (PTK-X), stimulates phosphorylation of the adaptor protein SHC [36]. This in turn recruits the Grb2-SOS complex and activates the MAPK pathway. 

Since then, a plethora of tyrosine-phosphorylated proteins has been discovered. Originally, tyrosine phosphorylation was believed to be involved primarily in regulating cell proliferation, since many oncogene products and growth factor receptors are protein tyrosine kinases (PTKs). However, it has become clear that tyrosine phosphorylation is involved in regulating a variety of cellular processes. In fact, the nervous system contains a large variety of PTKs and protein tyrosine phosphatases (PTPs), and some of these are exclusively expressed in neuronal tissues. Figure 24-1 shows the... 

FIGURE 24-2 Tyrosine phosphorylation and dephosphorylation. Protein tyrosine kinases (PTK) catalyze the transfer of the y-phosphate group from ATP to the hydroxyl group of tyrosine residues, whereas protein tyrosine phosphatases (PTP) remove the phosphate group from phosphotyro-sine. R, protein. 

Photoaffinity Labeling of Receptor Protein Tyrosine Kinases (PTK)... 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

Genistein (64), an isoflavone found in plants of the family Legu-minosae, is an inhibitor of several protein tyrosine kinases (PTK) and is currently in phase II clinical trials for its potential as an angiogenesis inhibitor. Genistein also has been utilized as a probe to identify binding sites for PTKs by observing the effect it demonstrates on cyclic-nucleotide-gated channels. ... 

T lymphocyte Kvl.3 potassium channels were also inhibited by genistein (42) in a protein tyrosine kinase (PTK)-independent way [290]. Daidzein (40) that was also studied in this work did not influence the properties of Kvl.3 potassium channels. The genistein-induced inhibition occurred much faster than was observed for neuronal Kvl.3 channels expressed in HEK293 cells [291], for which a PTK-dependent mechanism of genistein (42) action was proposed. On the other hand, PTK-independent inhibition of myocyte Kvl.3 channels by genistein (42) was reported by Washizuka et al. [292]. 

Signal transduction involves a transfer of information from cell surface receptors to the cytoplasm and ultimately to the nucleus where cellular activation and response are initated (1). Protein-tyrosine kinases (PTKs) serve central roles in many of these pathways by phosphorylating tyrosyl residues, which result in the introduction of phosphotyrosyl (pTyr, 1, Fig. 1) pharmacophores... 

The activation of cytokine receptors after ligands binding, provokes tyrosine phosphorylations by non-covalenty associated protein tyrosine kinases (PTKs) the Janus kinases (JAKs), a family that comprises JAKl, JAK 2, JAK 3 and TYR2. 

The most important pathways for transducing receptor activation by mitogens at the cell membrane into DNA synthesis and cell division involve PKC and protein tyrosine kinase (PTK). 

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