Signal transduction receptor protein kinases

Protein kinases are central to many signal-transduction pathways. Protein kinases are central to all three signal-transduction pathways described in this chapter. In the epinephrine-initiated pathway, cAMP-dependent protein kinase (PKA) lies at the end of the pathway, transducing information represented by an increase in cAMP concentration into covalent modifications that alter the activity of key metabolic enzymes. In the insulin- and EGF-initiated pathways, the receptors themselves are protein kinases and several additional protein kinases participate downstream in the pathways. Signal amplification due to protein kinase cascades are common features of each of these pathways and many others. Furthermore, protein kinases often phosphorylate multiple substrates, including many not considered herein, and by this means are able to generate a diversity of responses. 

Keywords Signal transduction, Photoaffinity labeling, G-Protein coupled receptors, Protein kinase, Tyrosine kinase, Aryl azide, Benzophenone, Diazirine... 

The multigene family of protein kinase C, which functions downstream of receptor protein kinases, is involved in the transduction of signals that regulate normal develop-... 

This stage involves alteration in gene expression and regulation via cell surface or cytosolic receptors. Most promoters affect gene expression via perturbation of the signal transduction pathways tyrosine kinase, steroid, or G protein linked. The result is cell proliferation. 

Althou the role of the MAP kinase phosphorylation cascade in the control of cell growth and cellular proliferation is undisputed, other pathways and pathway ramifications contribute to that control. This requires communication between signal transduction pathways. MAP kinase also seems to play a part in pathway interconnections, for example in connecting signals from G-protein-coupled receptors with signals from growth-factor-activated receptors (discussed in Chapter 5). 

The most important tools for intracellular signal transduction are the receptors, protein kinases, protein phosphatases, regulatory GTPases and adaptor proteins ... 

See also Viral and Cellular Oncogenes, Oncogenes in Human Tumors, G Proteins and Signal Transduction, G Protein Families and Subunits, Receptors with Protein Kinase Activity, Hormone Action... 

Fig. 11.11. Signal transduction by tyrosine kinase receptors. (1) Binding and dimerizaion. (2) Autophosphorylation. (3) Binding of Grb2 and SOS. (4) SOS is a GEF (guanine nucleotide exchange protein) that binds Ras, a monomeric G protein anchored to the plasma membrane. (5) GEE activates the exchange of GTP for bound GDP on Ras. (6) Activated Ras containing GTP binds the target enzyme Raf, thereby activating it.

Backlund M, Ingelman-Sundberg M. Regulation of aryl hydrocarbon receptor signal transduction by protein tyrosine kinases. Cell Signal 2005 17 39-48. 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

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