Disease relevance of STK38

• HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases [1].
• Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle [1].
• The DM group comprised 36 eyes with diabetic retinopathy (DR) and 55 without retinopathy (NDR) [2].
• Northern blot and immunohistochemistry analysis confirmed that gene and protein of brcaa1 displayed lower expression in normal gastric mucosa and higher expression in gastric cancer tissues, conversely, ndr1 displayed lower expression in gastric cancer and higher expression in normal gastric mucosa [3].

Psychiatry related information on STK38

• APOE genotypes were determined in 30 mild to moderate AD (83%) and mixed dementia (MIX, 17%), as well as in 11 nondemented first-degree relatives of AD (NDR), recruited from AD patient registry in Warsaw [4].

High impact information on STK38

• Members of the NDR (nuclear Dbf2-related) protein-kinase family are essential components of pathways that control important cellular processes, such as morphological changes, mitotic exit, cytokinesis, cell proliferation and apoptosis [5].
• Its induction also depends on the cognate host disease resistance gene RPS2 and the NDR1 gene that is required for RPS2-specified resistance [6].
• In vitro, MST3 selectively phosphorylated Thr442 of NDR2, resulting in a 10-fold stimulation of NDR activity [7].
• Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3 [7].
• Autophosphorylation of NDR is responsible for phosphorylation on Ser281/Ser282, whereas Thr444/Thr442 is targeted by an upstream kinase [7].

Biological context of STK38

• Previously, we demonstrated that the activity of NDR1 is controlled by phosphorylation of two regulatory residues, Ser-281 and Thr-444 [8].
• Nuclear Dbf2-related (NDR) protein kinases are a family of AGC group kinases that are involved in the regulation of cell division and cell morphology [9].
• Moreover, we found that NDR1 becomes activated through a direct interaction with EF-hand Ca(2+)-binding proteins of the S100 family [8].
• NDR protein kinases are involved in the regulation of cell cycle progression and morphology [7].
• A novel feature of NDR kinases is an insert within the catalytic domain between subdomains VII and VIII [10].

Anatomical context of STK38

• However, they differ in expression pattern; mouse Ndr1 is expressed mainly in spleen, lung and thymus, whereas mouse Ndr2 shows highest expression in the gastrointestinal tract [9].
• Significantly, the Ca(2+)-chelating agent BAPTA-AM suppressed the activity and phosphorylation of NDR1 on both Ser-281 and Thr-444, and specifically, these effects were reversed when we added the sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase pump inhibitor thapsigargin [8].
• Thus, to identify proteins that interact with NDR1 or NDR2, epitope-tagged kinases were immunoprecipitated from Jurkat T-cells [11].
• We provide insight into a potential in vivo mechanism of NDR activation through rapid recruitment to the plasma membrane mediated by hMOBs [12].
• Na+,K(+)-ATPase activity in erythrocytes was significantly lower in ND patients than in the NDR and F/CSS groups [13].

Associations of STK38 with chemical compounds

• NDR1 (nuclear Dbf2-related) is a serine/threonine protein kinase belonging to subfamily of kinases implicated in the regulation of cell division and morphology [8].
• NDR, a nuclear serine/threonine kinase, belongs to the subfamily of Dbf2 kinases that is critical to the morphology and proliferation of cells [14].
• Structure of the Ca(2+)/S100B/NDR Kinase Peptide Complex: Insights into S100 Target Specificity and Activation of the Kinase [15].
• The NDR shifts of HPAs obtained before and after pyridine adsorption were correlated with the acid strengths of the HPAs, suggesting that tunneling spectra measured by STM could serve to probe acid properties of HPAs [16].
• NDR animals rendered diabetic with streptozotocin were more responsive to insulin [17].

Other interactions of STK38

• We describe the cloning and characterization of the human and mouse NDR2, a second mammalian isoform of NDR protein kinase [9].
• We showed previously that NDR is regulated by phosphorylation and by the Ca(2+)-binding protein, S100B [10].

Analytical, diagnostic and therapeutic context of STK38

• Based on sequence analysis and in accordance to zebrafish orthologues we named the isolated genes Ndr1, Ndr2 and Spaw [18].
• The percentage reduction in the DR group was larger than in the NDR or control group [2].
• Therefore, the natural history of DR and rates of transition after treatment (including metabolic control and laser photocoagulation) from no diabetic retinopathy (NDR) to blindness were quantified [19].
• Two potential markers brcaa1 and ndr1 were identified by Western blot and immunohistochemistry [3].
• Fundus examination was performed by an ophthalmologist using an ophthalmoscope, and the findings were graded as: (1) no signs of diabetic retinopathy (NDR), (2) background diabetic retinopathy (BDR), or (3) proliferative diabetic retinopathy (PDR) [20].

References