Disease relevance of Klkb1

• These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS [1].
• Phylogenetic analysis of APS reductase amplicons obtained from the stomach, middle small intestine, and cecum of neonatal mice revealed that Desulfotomaculum spp. may be a predominant SRB group in the neonatal mouse intestine [2].
• The monoclonal antibody (mAb) SV5-Pk is used widely in a variety of procedures to detect recombinant proteins tagged with the Pk tag, a 14 amino acid sequence derived from the P and V proteins of the paramyxovirus Simian Virus 5 [3].
• The rat chondrosarcoma ATP sulfurylase and APS kinase activities, in fact, reside in a single bifunctional cytoplasmic protein, which has now been cloned and expressed [4].
• In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group [5].

High impact information on Klkb1

• Incorporation of 35SO42- into adenosine 5'-phosphosulfate (APS), 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and chondroitin sulfate was simultaneously assessed with extracts prepared from epiphyseal cartilage of neonatal normal or homozygous brachymorphic mice [6].
• Specific assays for ATP sulfurylase (sulfate adenylyltransferase; ATP:sulfate adenylyltransferase, EC 2.7.7.4) and APS kinase (adenylylsulfate kinase; ATP:adenylylsulfate 3'-phosphotransferase, EC 2.7.1.25) showed that the sulfurylase enzyme activity is reduced to approximately 1/2 and the kinase to approxomately 1/14 in brachymorphic mice [6].
• Radioactivity measured in APS, PAPS, and chondroitin sulfate of extracts from brachymorphic cartilage was approximately 300%, 9%, and 13% of the normal levels, respectively [6].
• APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance [7].
• Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads [7].

Chemical compound and disease context of Klkb1

• The increased incorporation of leucine in the kidney in APS-induced thrombocytopenia showed coincidence with increased thrombopoietin production [8].

Biological context of Klkb1

• We report the genetic map location of Kal3, bringing to 4 the number of genes with homologues on human 4q31-35 placed on the genetic map of mouse chromosome 8 [9].
• APS-facilitated phosphorylation occurred on tyrosines 371, 700, and 774 in the Cbl protein [10].
• Murine adenosine 3'-phosphate 5'-phosphosulfate (PAPS) synthetase consists of a COOH-terminal ATP-sulfurylase domain covalently linked through a nonhomologous intervening sequence to an NH2-terminal adenosine 5'-phosphosulfate (APS) kinase domain forming a bifunctional fused protein [11].
• A Cbl mutant incapable of dimerization failed to interact with APS and to undergo tyrosine phosphorylation in response to insulin, indicating an essential role of Cbl dimerization in these processes [12].
• Lastly, isotope dilution and enrichment experiments show directly that the APS binding sites of the mutant enzymes are more accessible to free APS than are those of the normal enzymes [13].

Anatomical context of Klkb1

• APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes [10].
• APS colocalized with filamentous actin (F-actin) accumulated during the capping of BCRs in APS-transgenic B cells [14].
• While experiments using cultured cell lines have demonstrated that APS is phosphorylated in response to various stimuli, its in vivo functions remain unclear [14].
• Moreover, the translocation of GLUT4 from intracellular vesicles to the plasma membrane was also inhibited by overexpression of the APS/Y(618)F mutant [10].
• Immunologically, APS(-/-) mice showed normal development and distribution of lymphocytes and myeloid cells, except for increased numbers of B-1 cells in the peritoneal cavity [14].

Associations of Klkb1 with chemical compounds

• APS is a Cbl-binding protein that is tyrosine phosphorylated by the insulin receptor kinase [10].
• Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice [15].
• Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated phosphorylation of adapter protein APS on serine 588 [16].
• Mutation of a highly conserved lysine in the P-loop to alanine (K65A) or arginine (K65R) or the following threonine (T66A) to alanine ablated APS kinase activity while leaving ATP-sulfurylase activity intact [17].
• Adenosine 5'-phosphosulfate (APS) kinase catalyzes the second reaction in the two-step conversion of inorganic sulfate to 3'-phosphoadenosine 5'-phosphosulfate (PAPS) [18].

Other interactions of Klkb1

• The Ant1 gene maps near Klk3 on proximal mouse chromosome 8 [19].
• A kallikrein gene (Kal3) was previously mapped by in situ hybridization to mouse chromosome 8 and human 4q35 [9].
• Clinical evaluation was performed, and two of the components of the kallikrein-kinin system, high-molecular-weight (HMW) kininogen and plasma prekallikrein, were assayed [20].

Analytical, diagnostic and therapeutic context of Klkb1

• Reverse transcriptase PCR analysis demonstrated APS reductase mRNA expression in all intestinal segments of 30-day-old mice, including the stomach [2].
• All the SV5-Pk mAbs can detect Pk tagged recombinant proteins in a variety of immunological procedures, including ELISA and immunofluorescence [3].
• Light and dark field autoradiography of semithin sections prepared 6 h after a treatment with APS showed that the incorporation of H3-leucine into the cells of the convoluted tubules of the kidney was increased in mice [8].
• The survival rates at the end of the dosing period were 73.3% (male) and 78.3% (female) in the control group, and 86.7-95.0% (male) and 86.7-91.7% (female) in the APS treated groups [5].

References