Signaling modules

Sigma (s-) receptors Signal flares Signaling smokes Signal modulators Signal processing... 

Linder JU, Schultz JOB (2003) The Class III adenylyl cyclases multi-purpose signalling modules. Cell Signal 15 1081-1089... 

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

MAP kinase signaling modules typically comprise a cassette of three protein kinases (Fig. 7.2A). For example, ERK (two isoforms in mammalian cells, ERK1/2) is phosphorylated (at Thr and Tyr residues in the activation loop of its catalytic domain by an upstream MAP kinase kinase (in this case, MEK) which is, in turn, phosphorylated and activated by a MAP kinase kinase kinase, in this instance, a member of the Raf group) (Fig. 7.2A). 

Figure 7.2 Organization of specific signaling modules. (A) The arrangement of upstream and downstream kinases in a typical MAP kinase module is shown, the named examples being from the classical MAP kinase (ERK) pathway. (B) The known composition of mTORCl and mTORC2 is shown.

Hoffmann, A., Levchenko, A., Scott, M. L and Baltimore, D. (2002) The IkappaB-NF-KappaB signaling module temporal control and selective gene activation. Science 298, 1241-1245. 

Figure 6.3. Schematic of interference fringe region, measurement volume, Doppler burst signals, and effects of particle size on signal modulation.

For data transfer applications the modulation speed of an emitter is a decisive parameter. Here the long lifetime of the excited state in PS becomes problematic. The fall time of the EL is usually in the ps regime, while somewhat shorter values are reported for the rise time. Only for devices based on OPS has a significantly shorter fall time (0.03 ps) been reported [WalO]. For small signal modulations of the EL from PS, frequencies in the order of 1 MHz are reported Ts4, Co5]. Such modulation frequencies are sufficient for display applications. For data transfer via optical interconnects, however, they are much too low. 

K. Dvorakova, H. Bernstein, C. Bernstein, H. Holubec and H. Garewal, Caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis protective role of the nitric oxide signalling module. Cell Biol. Toxicol, 2003, 19(6), 373. 

Most of the antibiotics commercially available nowadays are derivatives of natural compounds produced by bacteria or fungi. It is widely accepted that in nature these secondary metabolites can act as weapons for microbial cell defence, inhibiting the growth of competitors. However, it seems that antibiotics have, in nature, more sophisticated and complex functions [1-3]. Many environmental bacteria can not only cope with natural antimicrobial substances but also benefit from their presence. For instance, the use of antibiotics by bacteria as biochemical signals, modulators of metabolic activity or even carbon sources has been demonstrated [1, 2, 4]. In other cases, antibiotics can be tolerated because they have structures similar to the natural substrates of bacterial housekeeping enzymes and thus are inactivated, leading to a natural form of resistance [2]. These are just some... 

Fig. 3 A AGS proteins isolated in yeast-based functional screen G-protein signaling modulator (GPSM) as named by the Human Genome Nomenclature Committee. The major sites of action of AGS proteins in the context of the G-protein activation-deactivation cycle are indicated B on the right. (GPR G-protein regulatory, GEF guanine nucleotide exchange factor, GDI guanine nucleotide dissociation inhibitor, GPCR G-protein coupled receptor)...

The phase-shift fluorimeter on the other hand provides measurements of the phase angle and degree of modulation m relative to those of the excitation signal modulated at an angular frequency decay constants of both emitting species by Ax and A2 which are readily computed from the relationships... 

Whitmarsh, A.J. and Davis, R.J. Structural organization of MAP-kinase signaling modules by scaffold proteins in yeast and mammals (1998) Trends Biochem Sci 23, 481-485... 

Aplin, A.E., Howe, A., Alahari, S.K., Jiiliano, R.L. (1998) Signal transduction and signal modulation by cell adhesion receptors the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol. Rev. 50, 197-263. 

The multivalency of signaling proteins allows for the assembly of many different combinations of signaling modules, each combination presumably suited to particular signals, cell types, and metabolic circumstances. The large variety of protein kinases and of phosphoprotein-binding domains, each with its own specificity (the consensus sequence required in its substrate), provides for many permutations and combinations and many different signaling circuits of extraordinary complexity. And given the variety of specific phosphatases that reverse... 

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