minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila

Article (PDF Available)inNeuron 14(2):287-301 · March 1995with44 Reads
DOI: 10.1016/0896-6273(95)90286-4 · Source: PubMed
Abstract
The development of the adult central nervous system of Drosophila requires a precise and reproducible pattern of neuroblast proliferation during postembryonic neurogenesis. We show here that mutations in the minibrain (mnb) gene cause an abnormal spacing of neuroblasts in the outer proliferation center (opc) of larval brain, with the implication that mnb opc neuroblasts produce less neuronal progeny than do wild type. As a consequence, the adult mnb brain exhibits a specific and marked size reduction of the optic lobes and central brain hemispheres. The insufficient number of distinct neurons in mnb brains is correlated with specific abnormalities in visual and olfactory behavior. The mnb gene encodes a novel, cell type-specific serine-threonine protein kinase family that is expressed and required in distinct neuroblast proliferation centers during postembryonic neurogenesis. The mnb kinases share extensive sequence similarities with kinases involved in the regulation of cell division.
    • "Dual-specificity tyrosine-phosphorylation-regulated kinase, including dual-specificity yakrelated kinases (DYRKs) represent a large family of dual-specificity kinase, which can phosphorylate both Ser/Thr and Tyr substrates. To date, at least seven DYRK family members have been identified (DYRK1A, DYRK1B, DYRK1C, DYRK2, DYRK3, DYRK4A and DYRK4B) [1]. The DYRKs are evolutionarily conserved in their kinase domain, but differ from each other in the N-and C-terminal regions. "
    [Show abstract] [Hide abstract] ABSTRACT: Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer.
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    • "Among the genes from this 33-gene region, Dyrk1a is an attractive candidate for inducing cognitive impairment phenotypes. DYRK1A, the mammalian ortholog of Drosophila minibrain kinase (mnb) (Tejedor et al., 1995), encodes a proline/arginine-directed serine/threonine kinase. Both in trisomic mice and in individuals with DS, brain levels of DYRK1A are increased approximately 1.5-fold, indicating that this protein is overexpressed in a gene dosage-dependent manner (Dowjat et al., 2007). "
    Full-text · Dataset · Oct 2015 · Frontiers in Behavioral Neuroscience
    • "Among the genes from this 33-gene region, Dyrk1a is an attractive candidate for inducing cognitive impairment phenotypes. DYRK1A, the mammalian ortholog of Drosophila minibrain kinase (mnb) (Tejedor et al., 1995), encodes a proline/arginine-directed serine/threonine kinase. Both in trisomic mice and in individuals with DS, brain levels of DYRK1A are increased approximately 1.5-fold, indicating that this protein is overexpressed in a gene dosage-dependent manner (Dowjat et al., 2007). "
    [Show abstract] [Hide abstract] ABSTRACT: Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, potentially through GABA pathway. Some developmental and cognitive alterations have been traced to increased expression of the serine-threonine kinase DYRK1A on Hsa21. To better understand excitation/inhibition balance in DS, we investigated the consequences of long-term (1-month) treatment with EGCG-containing extracts in adult mBACtgDyrk1a mice that overexpress Dyrk1a. Administration of POL60 rescued components of GABAergic and glutamatergic pathways in cortex and hippocampus but not cerebellum. An intermediate dose (60 mg/kg) of decaffeinated green tea extract (MGTE) acted on components of both GABAergic and glutamatergic pathways and rescued behavioral deficits as demonstrated on the alternating paradigm, but did not rescue protein level of GABA-synthesizing GAD67. These results indicate that excessive synaptic inhibition in people with DS may be attributable, in large part, to increased DYRK1A dosage. Thus, controlling the level of active DYRK1A is a clear issue for DS therapy. This study also defines a panel of synaptic markers for further characterization of DS treatments in murine models.
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