Two component pathway

The two-component pathway was originaUy discovered in bacteria. It was only recently recognized that this kind of signal transduction is also used in eucaryotes. Bacteria possess signal systems which they use to react to changes in N availability, osmolarity and to chemotactic substances. The signaling pathway responsible for this regulation is... 

The two-component pathway is characterized by two functional elements. A histidine-specific protein kinase functions as a sensor that registers an external signal and passes this on to a downstream response regulator. The latter is activated by phosphorylation during the process of signal transduction, triggering other reactions in the cell (Fig. 12.3). 

The composition of the two-component pathway is very variable. The nature of the external signal and the reactions triggered in the cell may be very diverse. The sensor kinase may be a part of the receptor that registers the signal, or it may be on a polypeptide chain separate from the receptor. Furthermore, there are different mechanisms of coupling of the main functions of the two-component pathway. The sensor and reaction regulator may be on a single polypeptide or they may be on separate proteins. In addition, the proteins involved may be membrane proteins. 

Fig. 12.3. Principle of the two-component pathway. The fignre shows the principal steps of the two-component pathway in bacterial systems. An extraceUnlar signal (change in osmolarity, N availability, etc.) is registered by a receptor. An interaction takes place with the first component, the sensor kinase", which undergoes autophosphorylation at a His residue (H). The phosphate residue is transferred to the carboxyl side chain of an Asp residue (D) of the reaction regulator. Phosphorylation of the second component activates this for further signal conduction. The sen-sor kinase" may also be localized in the cytoplasmic domain of the receptor.

Fig. 12.4. Example of a two-component pathway in S. cerevisiae. Model of signal transdnction via the SLNl protein. The SLNl protein is a transmembrane protein with two transmembrane elements, which is assumed to exist as a dimer. The sensor domain and the regulator domain are localized on the same protein chain in the SLNl protein. The SLNl protein is activated by an extracellular signal (e.g., decrease in osmolarity). Autophosphorylation takes place on His (H) in the sensor domain and on Asp (D) in the regulator domain. A phosphate transfer takes place from the phosphohisti-dine to the effector protein SSKl. In the unphosphory-lated form, SSKl activates a MAPK pathway, which contains the protein kinase HOGl as a MAPK element. Various cellular reactions are triggered by HOGL If SSKl is phosphorylated in the course of activation of the two-component pathway, stimulation of the MAPK pathway is stopped. According to Swanson et al., (1994).

This system is employed by prokaryotic organisms, and homologous pathways have recently been identified in eukaryotes. The prototypical two-component pathway consists of two proteins A protein histidine kinase (sensor kinase) and a response regulator. Histidine kinases are very distinct from the superfamily of conventional protein serine/threonine and tyrosine kinases. The histidine kinases auto-phosphorylate on histidine residues and are involved in the phosphorylation of aspartate amino acids and their targets. 

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