Protein kinases signal transduction

Mikalsen T, Gerits N, Moens U (2006) Inhibitors of signal transduction protein kinases as targets for cancer therapy. Biotechnol Annu Rev 16 153-223... 

Signal transduction protein kinases, cKit, ras, MAPK, TRAIL... 

Bastiaens, P. I. and Jovin, T. M. (1996). Microspectroscopic imaging tracks the intracellular processing of a signal transduction protein fluorescent-labeled protein kinase C beta I. Proc. Natl. Acad. Sci. USA 93, 8407-12. 

In contrast to the receptors for insulin and growth factors (see p. 388), the cytokine receptors (with a few exceptions) have no tyrosine kinase activity. After binding of cytokine (1), they associate with one another to form homodimers, join together with other signal transduction proteins (STPs) to form dimers, or promote dimerization of other... 

Occurrence profiles involving functions, pathways, and other genomic data are used in comparative analysis in a way similar to that previously discussed for genes. For example, occurrence or abundance profiles of certain COGs (such as signal transduction histidine kinase, serine/threonine protein kinase, and phosphatase) can provide a broad overview of protein families present or absent in the genomes of interest, whereas occurrence profiles of Pfam domains found in these proteins could provide additional information on the signals sensed by the proteins. 

Once they are bound to an activated receptor, some signal-transduction proteins are phosphorylated by the receptor s intrinsic or associated kinase to achieve their active form. Binding of other signal-transduction proteins, present in the cytosol in unstimulated cells, positions them near their substrates localized in the plasma membrane. Both mechanisms can trigger downstream signaling. Several cytokine receptors (e.g., the IL-4 receptor) and RTKs (e.g., the insulin receptor)... 

A FIGURE 14-6 Recruitment of signal-transduction proteins to the cell membrane by binding to phosphotyrosine residues in activated receptors. Cytosolic proteins with SH2 (purple) or PTB (maroon) domains can bind to specific phosphotyrosine residues in activated RTKs (shown here) or cytokine receptors. In some cases, these signal-transduction proteins then are phosphorylated by the receptor s intrinsic or associated protein tyrosine kinase, enhancing their activity. 

Cloning of the genes identified by this procedure led to recognition of two key signal-transduction proteins a JAK tyrosine kinase and a STAT transcription factor. Subsequent work showed that one (sometimes two) of the four human... 

A FIGURE 14-26 Generation of phosphatidylinositol 3-phosphates. The enzyme phosphatidylinositol-3 kinase (PI-3 kinase) is recruited to the membrane by many activated receptor tyrosine kinases (RTKs) and cytokine receptors. The 3-phosphate added by this enzyme is a binding site for various signal-transduction proteins. [See L. Rameh and L. C. Cantley, 1999, J. Biol. Chem. 274 8347]... 

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