Disease relevance of BRSK2

• No anti-BRSK2 antibodies were found in the serum of 50 patients with SCLC without PNS, 19 with limbic encephalitis without onconeural antibodies, 50 with anti-Hu antibodies and several paraneoplastic neurological syndromes, including 14 with limbic encephalitis, and 160 with a variety of non-paraneoplastic neurological syndromes [1].
• We describe a new antigen, BR serine/threonine kinase 2 (BRSK2), identified by an antibody present in the serum of a patient with limbic encephalitis and small-cell lung cancer (SCLC) [1].
• The present study examines the cellular defects in vivo and pathologic changes observed in SAD-1 mice at atmospheric oxygenation as well as the effect of acute hypoxia [2].

High impact information on BRSK2

• A serine/threonine kinase SAD-1 in C. elegans regulates synapse development [3].
• Adult SAD-1 transgenic mice were not anemic but had some abnormal features of erythrocytes and slightly enlarged spleens [4].
• In earlier work, we showed that Sad1, the gene encoding the first committed enzyme in the avenacin pathway (beta-amyrin synthase), had arisen by duplication and divergence of a cycloartenol synthase-like gene [5].
• We also demonstrate that two sodium azide-generated saponin-deficient mutants of oat, which define the Sad1 genetic complementation group, are defective in the gene encoding this enzyme and provide molecular genetic evidence indicating a direct link between AsbAS1, triterpenoid saponin biosynthesis, and disease resistance [6].
• The predicted hsSAD1 protein comprises 778 amino acids and shares significant homology with the fission yeast Cdr2, a mitosis-regulatory kinase, and Caenorhabditis elegans SAD1, a neuronal cell polarity regulator [7].

Biological context of BRSK2

• Furthermore, our study indicated that the kinase activity of BRSK2 can be increased through phosphorylation by PKA [8].
• Less than 1% recombination was observed between Glu1 (on chromosome 10) and Sad1 [9].

Anatomical context of BRSK2

• Eluted IgG from the BRSK2 clone gave a similar immunolabeling than the patient's serum by immunohistochemistry and immunoblot of rat brain and testis [1].
• Probing a rat hippocampus expression library with the patient's serum resulted in the isolation of BR serine/threonine kinase 2 (BRSK2), a protein (also know as SAD1B kinase) preferentially expressed in the brain and testis and implicated in neuronal polarization as well as synaptic development [1].
• In one of the five transgenic lines obtained, SAD-1, red blood cells contained 19% human Hb SAD (alpha 2 human 1 beta 2SAD) and mouse-human hybrids in addition to mouse hemoglobin [4].

Associations of BRSK2 with chemical compounds

• BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260 [8].
• Treatment with dithiothreitol reduced K(+)-Cl- cotransport activity in SAD-1 and beta-thal/SAD-1 mice to levels similar to that of control strains, indicating that reversible sulfhydryl oxidation contributes to the activated state of K(+)-Cl- cotransport in mouse erythrocytes that express transgenic human Hb SAD [10].

Enzymatic interactions of BRSK2

• LKB1 can phosphorylate the Thr174 of BRSK2, increasing its activity >50-fold [8].

Other interactions of BRSK2

• Our study suggests BRSK2 may be an autoantigen involved in the pathogenesis of SCLC-associated limbic encephalitis [1].

References