Serine/threonine-protein kinase-11
InterPro Protein Domain record
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description
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<p>Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [<cite idref="PUB00005115"/>]:</p><p> <ul> <li>Serine/threonine-protein kinases</li><li>Tyrosine-protein kinases</li><li>Dual specific protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)</li> </ul> </p><p>Protein kinase function has been evolutionarily conserved from <taxon tax_id="562">Escherichia coli</taxon> to human [<cite idref="PUB00020114"/>]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [<cite idref="PUB00015362"/>]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [<cite idref="PUB00034898"/>], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [<cite idref="PUB00034899"/>].</p><p>The LKB1 (also called serine/threonine kinase 11) tumour suppressor gene was cloned by linkage analysis of Peutz-Jeghers cancer syndrome patients [<cite idref="PUB00034863"/>]. Mammalian LKB1 has been implicated as a regulator of multiple biological processes and signalling pathways, including the control of cell-cycle arrest, p53-mediated apoptosis, Wnt signalling, transforming growth factor (TGF)-beta signalling, ras-induced cell transformation, and energy metabolism [<cite idref="PUB00034864"/>]. The <taxon tax_id="6239">Caenorhabditis elegans</taxon> and <taxon tax_id="7227">Drosophila melanogaster</taxon> LKB1 homologs, termed PAR4 and dLKB1, respectively, regulate cell polarity.</p> <p>Lkb1(+/-) mice develop intestinal polyps identical to those seen in individuals affected with PJS [<cite idref="PUB00034865"/>]. Consistent with this in vivo tumour suppressor function, Lkb1 deficiency prevents culture-induced senescence without loss of Ink4a/Arf or p53. Despite compromised mortality, Lkb1(-/-) mouse embryonic fibroblasts show resistance to transformation by activated Ha-Ras either alone or with immortalizing oncogenes. This phenotype is in agreement with the paucity of mutations in Ras seen in PJS polyps and suggests that loss of Lkb1 function as an early neoplastic event renders cells resistant to subsequent oncogene-induced transformation.</p> <p>LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signalling downstream of mTOR [<cite idref="PUB00034866"/>].</p>
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Serine/threonine-protein kinase-11
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InterPro Protein Domain record
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