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The genomic organization of the coding sequence of the LKB gene is shown on the top, and the functional domains of the protein are shown below with frameshift mutations.Therefore, RSK and PKA may regulate cell growth through phosphorylation of LKB.It would be of interest to explore whether LKB could play a role in mediating DNA damage responses in cells.Mass spectrometry analysis revealed that the form of prenylation on LKB was farnesylation rather than geranylgeranylation. However, the mechanism by which prenylation regulates LKB is unknown.There are two closely related isoforms of STRAD termed STRAD and STRAD, which possess high sequence homology to the STE family of protein kinases but lack several key catalytic residues required for catalysis and have therefore been classied as pseudokinases.STRAD is inactive and does not autophosphorylate or phosphorylate any <a href="https://www.ncbi.nlm.nih.gov/pubmed/22634637">Targetmol's Fructose</a> substrate tested. There are also two isoforms of MO, known as MO and MO, that, although closely related to each other, bear no sequence homology to any other protein in the database.LKB, when overexpressed on its own in mammalian cells, is localized mainly in the nucleus, although a small fraction was reproducibly found in the cytoplasm. This is also consistent with the nding that no point mutations in this region of LKB have been reported in human cancers. Also supporting this conclusion is the nding that mutants of LKB, which are unable to enter the nucleus, still suppress cell growth in overexpression studies. STRAD and MO when expressed alone in cells are both localized throughout the cytoplasm and nucleus, but they are only localized in the cytoplasm and excluded from the nucleus when expressed together.Interestingly, when LKB is expressed with STRAD and MO, it becomes strikingly relocalized in the cytoplasm. Point mutants of LKB found in human cancers, which are   unable to interact with STRAD and MO, remain localized exclusively within the nucleus when expressed in cells. Additional mechanisms may also exist to maintain LKB in the cell cytoplasm.The interaction of LKB with a protein called LKB interacting protein. Whether LIP can interact with the heterotrimeric LKB:STRAD:MO complex has not been tested.The catalytic activity of LKB toward myelin basic protein is increased fold in the presence of STRAD and MO isoforms, indicating that these subunits activated LKB. The pseudokinase domain of STRAD isoforms binds directly to the kinase domain of LKB.There are likely to be multiple sites of interaction between LKB catalytic and STRAD pseudokinase domain because PJS point mutations, located within different regions of the LKB catalytic domain, abolished interaction with STRAD:MO. Mutation of any of these three residues abolishes the ability of MO to bind STRAD. This indicates that interaction of LKB with STRAD creates an additional binding site for either MO or LKB within the complex, which may explain why MO stabilizes the binding of LKB to STRAD.However, it will be necessary to crystallize the entire LKB:STRAD:MO complex in order to understand in full the molecular mechanism by which these proteins interact.In addition to interacting with STRAD and MO isoforms, a signicant pool of cellular LKB is associated with a chaperone complex consisting of heat shock protein.

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