Signaling/signal transduction

L. V. Dekker and A. W. Segal. Signal transduction signals to move cells. Science, 287, 982—985, 2000. 

The protein kinases are a family of proteins (serine/threonine kinases and tyrosine kinases) involved in signal transduction. Signal transduction via these proteins occurs through selective and reversible phosphorylation of... 

Components of Intracellular Signal Transduction Signaling Proteins... 

Calculation of Conformational Free Energies for a Model of a Bilobal Enzyme Protein kinases catalyze the transfer of phosphate from adenosine triphosphate (ATP) to protein substrates and are regulatory elements of most known pathways of signal transduction. 

The spatial and steric requirements for high affinity binding to protein kinase C (PKC), a macromolecule that has not yet been crystallized, were determined. Protein kinase C plays a critical role in cellular signal transduction and is in part responsible for cell differentiation. PKC was identified as the macromolecular target for the potent tumor-promoting phorbol esters (25). The natural agonists for PKC are diacylglycerols (DAG) (26). The arrows denote possible sites of interaction. 

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. 

A Biosensor is a device where a coupling has been realized between a biological element responsible for the molecular recognition and tire element responsible for the transduction of the signal. 

In this chapter we describe some examples of structures of membrane-bound proteins known to high resolution, and outline how the elucidation of these structures has contributed to understanding the specific function of these proteins, as well as some general principles for the construction of membrane-bound proteins. In Chapter 13 we describe some examples of the domain organization of receptor families and their associated proteins involved in signal transduction through the membrane. 

The augmentation of a p sheet in one protein by a strand emanating from another is a mode of protein association not restricted to viral shells. Small domains involved in intracellular signal transduction bind to "arms" of other proteins by presenting the edge of a sheet on which those arms can form an additional strand. 

Depletion of ATP in the cells prevents maintenance of the membrane potential, inhibits the functioning of ion pumps, and attenuates cellular signal transduction (e.g., formation of second messengers such as inositol phos phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-itv of the cell and leads to ceil death. 

Felder, C. C. (1995). Muscarinic acetylcholine receptors . Signal transduction through multiple effectors. FASEB j. 9, 619-625. 

Cells make use of many different types of membranes. All cells have a cytoplasmic membrane, or plasma membrane, that functions (in part) to separate the cytoplasm from the surroundings. In the early days of biochemistry, the plasma membrane was not accorded many functions other than this one of partition. We now know that the plasma membrane is also responsible for (1) the exclusion of certain toxic ions and molecules from the cell, (2) the accumulation of cell nutrients, and (3) energy transduction. It functions in (4) cell locomotion, (5) reproduction, (6) signal transduction processes, and (7) interactions with molecules or other cells in the vicinity. 

Airother interesting facet of lipid anchors is that they are transient. Lipid anchors can be reversibly attached to and detached from proteins. This provides a switching device for altering the affinity of a protein for the membrane. Reversible lipid anchoring is one factor in the control of signal transduction pathways in eukaryotic cells (Chapter 34). 

Thiophene, 2,2-bithiophene, and 2,2, 5, 2"-terthiophene derivatives from Chinese medicinal plants as oncogene signal transduction inhibitors (proteinki-nase C inhibitors) 99PAC1101. 

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