Explain the roles of protein kinase and protein phosphatase in the regulation of

Question

Explain the roles of protein kinase and protein phosphatase in the regulation of signaling pathways involving phosphate-regulated molecular switches. Explain the roles of GAPs and GEFs in the regulation signaling pathways involving GTP-binding proteins. Explain the roles of adenylyl cyclase and cyclic AMP phosphodiesterase in the regulation of cAMP signaling pathways. Explain why, in all three of these examples, prompt inactivation of these signaling molecules is necessary for rapid signaling to occur.

Explanation / Answer

In the signalling pathway a specific pathway is activated by the addition or deletion of phosphate group to the enzyme that is involved in the pathway. So , for the addition of phosphate group to an enzyme protein kinase is used and for the deletion of phosphate group then protein phosphatase is used. Some of the proteins are activated only when it is bound to GTP , for example RAS proteins. GAPs are GTPase activating proteins. and GEFs are Guanine nucleotide exchange factors . GAPs function to attach GTPs to the protein and GEFs function to inactivate the protein by dissociating GTP and enabling binding of GDP. If there the RAS protein turns to an oncogene this GEFs will not function and the GTP is constantly bound to the RAS and it is constantly activate leading to continuous proliferation of cells which ultimately leads to tumour. cAMP is an important second messenger . It is activated by the enzyme adenylate cyclase and deactivated by phosphodiesterase. Adenylate cyclase is activated by G protein coupled receptors. When a G alpha subunit dissociates from the trimer Galpha beta gamma subunits , the G beta gamma activates adenyl cyclase which inturn activates cAMP . This cAMP activates various protein kinases and thereby these protein kinases add phosphate groups to the target molecules thereby enabling cell proliferation. When the Gi subunit attaches to the G protein coupled receptors then the Adenylyl cyclase pathway is deactivated and phosphodiesterase is activated and hence cAMP pathway is inhibited thus the protein kinase cannot be activated and target molecules cannot be phosphorylated. Hence this signal is opposite to adenylate cyclase activation . All the above 3 pathways described , both positively and negatively regulate the cell proliferation and differentiation. protein kinase ( positive ) and protein pathway ( negative ) GAPs ( positive) GEFs (negative) Adenylate cyclase (positive ) and Phosphodiestrease ( negative) If any of the pathway is activated continuously without negative control then it results in tumour formation. If any pathway is constantly in negative state a proper protein cannot be formed thereby cell differentiation cannot take place. Hence both positive and negative controls should work coordinatively to establish proper development of the cells and tissues.

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