Signal transduction protein substrates

An example of the signal-transduction protein-targeted inhibitor design which illustrates both peptide scaffold- and nonpeptide template-based approaches is that for the Ras famesyl transferase inhibitor discovery. Such compounds show potential as new therapeutic agents for Ras-related carcinogenesis [81]. Substrate sequences for famesyl transferase have the consensus Cy s-A A, - A A2-Met motif (AA refers to Val or lie). Both substrate-based... 

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)... 

Protein-ligand interactions are important phenomena that touch upon every facet of biological functions. These include such examples as enzyme-substrate interactions in biochemical transformations, transducer-membrane interactions in signal transduction, protein-nucleic acid interactions in genetic transmission, protein-carbohydrate interactions in cell adhesion as well as protein-protein interactions in biochemical regulations and defense (immune response). Databases of interacting proteins are available respectively at DIP (http //dip.doe-mbi.ucla.edu) and IntAct project of EBI (http //ebi.ac.uk/intact). 

EUehauge, E., Norregaard-Madsen, M. and Sogaard-Andersen, L. (1998). The FruA signal transduction protein provides a checkpoint for the temporal coordination of intercellular signals in M. xanthus development. Md. Microbiol. 30, 807-817. Fontes, M. and Kaiser, D. (1999). Myxococcus cells respond to elastic forces in their substrate. Proc. Natl. Acad. Sci. U.S.A. 96, 8052-8057. 

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. 

Histidine phosphatases and aspartate phosphatases are well established in lower organisms, mainly in bacteria and in context with two-component-systems . Reversible phosphorylation of histidine residues in vertebrates is in its infancy. The first protein histidine phosphatase (PHP) from mammalian origin was identified just recently. The soluble 14 kD protein does not resemble any of the other phosphatases. ATP-citrate lyase and the (3-subunit of heterotrimeric GTP-binding proteins are substrates of PHP thus touching both, metabolic pathways and signal transduction [4]. 

Numerous studies have shown that EGF binding to EGFR triggers receptor dimerization. This is considered a crucial step in intracellular signal transduction [98]. Inspired by this mechanism, we designed EGF chimeric proteins that spontaneously dimerized (dEGF-His). These dimers were terminally anchored to the substrate. We expected that these preformed dimeric EGF structures would facilitate the formation of EGF-EGFR dimer complexes more efficiently than monomeric EGF structures. 

The brain contains many other types of second-messenger-independent protein kinases. Examples of other second-messenger-independent protein kinases are listed in Table 23-1. Many of these include enzymes that were identified originally in association with a particular substrate protein but shown later to play a more widespread role in brain signal transduction. The functional role of one of these, [3-adrenergic receptor kinase (PARK), a type of G protein receptor kinase (GRK), is discussed further below. 

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