The MurineDyrkProtein Maps to Chromosome 16, Localizes to the Nucleus, and Can Form Multimers

Song, Woo-Joo; Chung, Samuel; Kurnit, David M.

doi:10.1006/bbrc.1997.6154

Cited by 38 publications

(19 citation statements)

References 21 publications

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“…Despite the similar molecular design of these kinases, the N-terminal and the long C-terminal domains of ANPK appear unique and share no significant homology with Yak1, MNB, or any other characterized protein kinase. Similar to the minibrain gene product (Song et al, 1997), both transiently expressed Figure 8. Colocalization of AR and ANPK in CV-1 cell nuclei.…”

Section: Discussionmentioning

confidence: 99%

Activation of Androgen Receptor Function by a Novel Nuclear Protein Kinase

Moilanen¹,

Karvonen²,

Poukka³

et al. 1998

MBoC

101

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Androgen receptor (AR) belongs to the nuclear receptor superfamily and mediates the biological actions of male sex steroids. In this work, we have characterized a novel 130-kDa Ser/Thr protein kinase ANPK that interacts with the zinc finger region of AR in vivo and in vitro. The catalytic kinase domain of ANPK shares considerable sequence similarity with the minibrain gene product, a protein kinase suggested to contribute to learning defects associated with Down syndrome. However, the rest of ANPK sequence, including the AR-interacting interface, exhibits no apparent homology with other proteins. ANPK is a nuclear protein that is widely expressed in mammalian tissues. Its overexpression enhances AR-dependent transcription in various cell lines. In addition to the zinc finger region, ligand-binding domain and activation function AF1 of AR are needed, as the activity of AR mutants devoid of these domains was not influenced by ANPK. The receptor protein does not appear to be a substrate for ANPK in vitro, and overexpression of ANPK does not increase the extent of AR phosphorylation in vivo. In view of this, it is likely that ANPK-mediated activation of AR function is exerted through modification of AR-associated proteins, such as coregulatory factors, and/or through stabilization of the receptor protein against degradation. INTRODUCTIONThe androgen receptor (AR) mediates the biological actions of physiological androgens (Quigley et al., 1995). DNA-bound transcription factors, such as AR and other nuclear receptors, have been postulated to stimulate the efficiency of transcription by affecting directly or indirectly the assembly of basal transcription factors into the preinitiation complex, thereby increasing the rate of transcription initiation (Tjian and Maniatis, 1994;Horwitz et al., 1996;Beato and Sanchez-Pacheco, 1996). However, regulation of receptor function also involves cross-talk with other signaling pathways and interactions with other transcription factors and coregulatory proteins (Beato et al., 1995). Although nuclear receptors may contact directly some members of the basal transcription machinery (Ing et al., 1992;Blanco et al., 1995;Hadzig et al., 1995;Schulman et al., 1995;McEwan and Gustafsson, 1997) or TATA-binding protein-associated factors (Jacq et al., 1994;Schwerk et al., 1995; Mengus et al., 1997), they appear to employ preferentially coregulators to interact with the transcription machinery (Beato and Sanchez-Pacheco 1996;Horwitz et al., 1996). Examples of the coregulators include RIP-140 (Cavaillés et al., 1995), TIF1 (Le Douarin et al., 1995), TRIP1/SUG1 (Lee et al., 1995;vom Baur et al., 1996), ARA 70 (Yeh and Chang, 1996), CBP/p300 (Chakravarti et al., 1996;Hanstein et al., 1996;Kamei et al., 1996), and SRC-1 (Oñ ate et al., 1995) and its variants or related proteins, such as GRIP1, TIF2, AIB1, and TRAM-1 (Hong et al., 1996;Voegel et al., 1996;Anzick et al., 1997;Takeshita et al., 1997). Most of the these coregulators have been discovered through protein-protein interaction screening ...

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Section: Discussionmentioning

confidence: 99%

Activation of Androgen Receptor Function by a Novel Nuclear Protein Kinase

Moilanen¹,

Karvonen²,

Poukka³

et al. 1998

MBoC

101

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“…21 is ongoing. The Tiam1 gene, which is nonrecombinant with Cbr1 and Dyrk on a commonly used backcross mapping panel (Song et al 1997), was not found on the contig and hence must lie proximal to Cbr1.…”

Section: Transcriptsmentioning

confidence: 99%

Physical and Comparative Mapping of Distal Mouse Chromosome 16

Cabin¹,

McKee-Johnson²,

Matesic³

et al. 1998

Genome Res.

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Distal mouse Chromosome 16 (Chr. 16) includes a region of conserved linkage with human Chromosome 21 (Chr. 21). Mouse models of Down syndrome based on trisomy of distal Chr. 16 have several phenotypes similar to those seen in human patients and have proven useful for correlating dosage imbalance of specific genes with specific developmental anomalies. The degree to which such findings can be related to Down syndrome depends on how well the conserved synteny is maintained. Twenty-four genes have been mapped in both species and there are no discordancies, but the region could carry hundreds of genes. Comparative sequence represents the ultimate comparative map and will aid in identification of genes and their regulatory sequences. A physical map of the distal 4.5 Mb of Chr. 16 has been assembled as an essential step toward a map of sequence-ready templates. The map consists of 51 YACs and 15 BACs and includes 18 transcripts, 9 of which are mapped for the first time in mouse, and 3 of which are, for the first time, described in either species. YAC fragmentation was used to precisely localize the 49 markers on the map. Comparison of this physical map with that of the corresponding region on Chr. 21 shows conservation not only of gene order but of size in the 3 Mb fromCbr1 to Ets2; distal to Ets2, the human map is expanded.[The sequence data described in this paper have been submitted to GenBank. See Tables 1 and 2 for accession nos.]

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“…This is caused by the abnormal spacing of neuroblasts and a reduction in the production of neuronal progeny (Tejedor et al, 1995). At least seven closely related homologous mammalian kinases in the DYRK family have since been isolated (Guimera et al, 1996(Guimera et al, , 1999Shindoh et al, 1996;Song et al, 1996Song et al, , 1997Raich et al, 2003). The DYRK family possesses serine and threonine phosphorylation activity as well as autophosphorylation activity on tyrosine residues (Kentrup et al, 1996;Becker et al, 1998;Becker and Joost, 1999;Himpel et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

DYRK1A Enhances the Mitogen-activated Protein Kinase Cascade in PC12 Cells by Forming a Complex with Ras, B-Raf, and MEK1

Kelly

Rahmani

2005

MBoC

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Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) is the human homologue of the Drosophila mnb (minibrain) gene. In Drosophila, mnb is involved in postembryonic neurogenesis. In human, DYRK1A maps within the Down syndrome critical region of chromosome 21 and is overexpressed in Down syndrome embryonic brain. Despite its potential involvement in the neurobiological alterations observed in Down syndrome patients, the biological functions of the serine/threonine kinase DYRK1A have not been identified yet. Here, we report that DYRK1A overexpression potentiates nerve growth factor (NGF)-mediated PC12 neuronal differentiation by up-regulating the Ras/MAP kinase signaling pathway independently of its kinase activity. Furthermore, we show that DYRK1A prolongs the kinetics of ERK activation by interacting with Ras, B-Raf, and MEK1 to facilitate the formation of a Ras/B-Raf/MEK1 multiprotein complex. These data indicate that DYRK1A may play a critical role in Ras-dependent transducing signals that are required for promoting or maintaining neuronal differentiation and suggest that overexpression of DYRK1A may contribute to the neurological abnormalities observed in Down syndrome patients. INTRODUCTIONMinibrain (mnb)/dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) gene is a member of a growing family of protein kinases called DYRK. In Drosophila, mnb seems to play an essential role during postembryonic neurogenesis. Mutant flies are characterized by a marked reduction in size of the adult optic lobes and the central brain hemispheres. This is caused by the abnormal spacing of neuroblasts and a reduction in the production of neuronal progeny (Tejedor et al., 1995). At least seven closely related homologous mammalian kinases in the DYRK family have since been isolated (Guimera et al., 1996(Guimera et al., , 1999Shindoh et al., 1996;Song et al., 1996Song et al., , 1997Raich et al., 2003). The DYRK family possesses serine and threonine phosphorylation activity as well as autophosphorylation activity on tyrosine residues (Kentrup et al., 1996;Becker et al., 1998;Becker and Joost, 1999;Himpel et al., 2000). Their kinase activity is dependent on the YXY motif in the activation loop of the catalytic domain, which is located at the same position as the characteristic TXY motif of the mitogen-activated protein kinases (MAPKs), suggesting an activation mechanism similar to that of the MAPK (Himpel et al., 2000). Closely related enzymes in lower eukaryotes also have been isolated, including Yak1p in Saccharomyces cerevisiae (Garrett and Broach, 1989), Pom1p in Schizosaccharomyces pombe (Bahler and Pringle, 1998), and YakA in Dictyostelium discoideum (Van Es et al., 2001). Although not much is known about their cellular functions, they all seem to be involved in the regulation of the cell growth and/or development.In the DYRK family, DYRK1A has been the best characterized to date. The human Dyrk1A gene maps to the 21q22.2 region of chromosome 21, in the Down syndrome critical region (Rah...

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The MurineDyrkProtein Maps to Chromosome 16, Localizes to the Nucleus, and Can Form Multimers

Cited by 38 publications

References 21 publications

Activation of Androgen Receptor Function by a Novel Nuclear Protein Kinase

Activation of Androgen Receptor Function by a Novel Nuclear Protein Kinase

Physical and Comparative Mapping of Distal Mouse Chromosome 16

DYRK1A Enhances the Mitogen-activated Protein Kinase Cascade in PC12 Cells by Forming a Complex with Ras, B-Raf, and MEK1

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