Three Dact gene family members are expressed during embryonic development and in the adult brains of mice

Fisher, Daniel A.C.; Kivimäe, Saul; Hoshino, J.; Suriben, Rowena; Martin, P.; Baxter, Nichol; Cheyette, Benjamin N.R.

doi:10.1002/dvdy.20917

Cited by 69 publications

(114 citation statements)

References 31 publications

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“…Three Dpr family members, Dpr1, Dpr2, and Dpr3, have been described in mammals (23), and they appear to have distinct functions. Human Dpr1 as well as Dpr3 can inhibit Wnt signaling by promoting Dvl degradation (14,24,25).…”

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confidence: 99%

Protein Kinase A-mediated 14-3-3 Association Impedes Human Dapper1 to Promote Dishevelled Degradation

Hua

Martin

et al. 2011

Journal of Biological Chemistry

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Wnt signaling regulates embryo development and tissue homeostasis, and its deregulation leads to an array of diseases, including cancer. Dapper1 has been shown to be a key negative regulator of Wnt signaling. However, its function and regulation remain poorly understood. In this study, we report that 14-3-3␤ interacts with human Dapper1 (hDpr1). The interaction is dependent on protein kinase A (PKA)-mediated phosphorylation of hDpr1 at Ser-237 and Ser-827. 14-3-3␤ binding attenuates the ability of hDpr1 to promote Dishevelled (Dvl) degradation, thus enhancing Wnt signaling. We further provide evidence that PKA-mediated Dpr1 phosphorylation may contribute to growth and tumor formation of colon cancer Caco2 cells. Finally, we show that cyclooxygenase-2 expression and PKA activation are positively correlated with Dvl protein levels in colon cancer samples. Together, our findings establish a novel layer of regulation of Wnt signaling by PKA via the 14-3-3-Dpr1-Dvl axis.Both the canonical and noncanonical Wnt signaling pathways are evolutionarily conserved and play key roles in development and disease (1-4). The canonical Wnt/␤-catenin pathway is initiated by Wnt ligands binding to their receptors Frizzled and low density lipoprotein receptor-related protein 5/6 (LRP5/6), which leads to the cytosolic accumulation of ␤-catenin by disrupting the ␤-catenin destruction complex consisting of Axin, adenomatous polyposis coli (APC), 3 and glycogen synthase kinase 3␤ (GSK3␤). Accumulated ␤-catenin translocates into the nucleus and activates the transcription of Wnt target genes in collaboration with the transcription factor T cell factor/lymphoid enhancer factor (5, 6). In addition to the planar cell polarity (PCP) pathway, which regulates cell polarity and convergent extension, noncanonical Wnt signaling can also be mediated by Ca 2ϩ and other signaling molecules (7,8).Dishevelled (Dvl) is the central player in both the canonical and noncanonical Wnt signaling pathways, serving as a scaffold protein bridging . Dvl can also function in the nucleus (11), where it cooperates with c-Jun, ␤-catenin, and TCF to regulate Wnt target gene transcription (12). Therefore, like many other signaling proteins, Dvl activity is tightly regulated. It can be phosphorylated by casein kinase 2 (13). The stability of Dvl proteins is regulated by an array of proteins, including Dapper1/Dact1, Inversin, NEDL1, Prickle-1, and KLHL12 (14 -17). Our recent work also showed that Dvl protein is ubiquitinated by pVHL-containing E3 ubiquitin ligase and can be regulated by autophagy (18). In addition, altered Dvl expression has been implicated in oncogenesis. Dvl is overexpressed in prostate cancer, non-small cell lung cancer, mesothelioma, and other cancers, and its up-regulation has been indicated to be correlated with activation of Wnt/␤-catenin signaling (19 -21).Dapper1 (Dpr1), also called Dact1, as a Dvl-interacting protein, is a negative regulator of both canonical and noncanonical Wnt signaling (14,22). Three Dpr family members, Dpr1, Dpr2, and Dpr...

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Protein Kinase A-mediated 14-3-3 Association Impedes Human Dapper1 to Promote Dishevelled Degradation

Hua

Martin

et al. 2011

Journal of Biological Chemistry

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“…Three Dact family members (Dact1-3) have been identified in vertebrates (25), where based on a variety of in vitro and in vivo assays, they appear to have both overlapping and divergent signaling functions (26 -31). In studies using genetically engineered mice, we have shown previously that Dact1 is required for normal post-translational regulation of Vangl2 during the epithelial-mesenchymal transition at the primitive streak, for normal PCP in posterior embryonic tissues, and that defects in these developmental processes in Dact1 null embryos lead to complex birth malformations, including NTDs (29).…”

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SEC14 and Spectrin Domains 1 (Sestd1) and Dapper Antagonist of Catenin 1 (Dact1) Scaffold Proteins Cooperatively Regulate the Van Gogh-like 2 (Vangl2) Four-pass Transmembrane Protein and Planar Cell Polarity (PCP) Pathway during Embryonic Development in Mice

Yang

Cheyette

2013

Journal of Biological Chemistry

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“…The importance of this range, which would allow students to be active, focused, and engaged, has been addressed from a variety of theoretical perspectives-the Zone of Proximal Development (Vygotsky, 1978), functional-optimal performance (Fischer & Bidell, 2006), and Flow (Csikszentmihalyi & Rathund, 1998). During the first two years that we taught the course, the questionnaires evolved in minor ways, mostly to increase the clarity of the questions.…”

Section: Methodsmentioning

confidence: 99%

“…Howe, Devine and Tavares (2013) summarized three potential issues with the classic framework when researchers reported limited success with an intervention: "(a) experiments often fail to generate the requisite data; (b) Posner et al's (1982) [first] three conditions may be necessary, but they are insufficient; and, (c) cognitive limitations eclipse the significance of experimental evidence" (p. 865). The last point has been a central focus in the cognitive sciences to understand cognitive limitations from a developmental point of view and to explain the movement from disequilibrium to equilibrium as a dynamic process that evolves as the mind and brain mature (Fischer & Bidell, 2006;Schwartz, 2009).…”

Section: Literature Reviewmentioning

confidence: 99%

Confronting the Need for Conceptual Change in Pre-Service Science Education

Schwartz¹,

Shapiro²,

Gregory³

2013

HES

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During a five-year period the authors taught over 100 students in a graduate course (The Nature of Science) counting toward teacher certification at the Harvard Graduate School of Education. Despite the fact that students had undergraduate degrees in the sciences, most of them found the application of models in science challenging and the epistemological consequences unsettling. Moreover, students found it especially difficult to use a model to correctly generate predictions, which was starkly illustrated with the application of Archimedes' principle during our unit on floating and sinking. We examine the deceptive belief that student success with algorithms and word problems leads to conceptual understanding as well as the conceptual change necessary to understand the relationship between evidence and inference as explored in the nature of science course. Considering the apparently strong science backgrounds of our students, we doubt that typical pre-college students can achieve the goals described in the National Science Education Standards in the short time typically allotted for their science studies. We explore the issues students face in "understanding" science as well as the impact of science education on students and teachers, and implications for policy makers and pre-service programs.

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Three Dact gene family members are expressed during embryonic development and in the adult brains of mice

Abstract: Members of the

Cited by 69 publications

References 31 publications

Protein Kinase A-mediated 14-3-3 Association Impedes Human Dapper1 to Promote Dishevelled Degradation

Protein Kinase A-mediated 14-3-3 Association Impedes Human Dapper1 to Promote Dishevelled Degradation

SEC14 and Spectrin Domains 1 (Sestd1) and Dapper Antagonist of Catenin 1 (Dact1) Scaffold Proteins Cooperatively Regulate the Van Gogh-like 2 (Vangl2) Four-pass Transmembrane Protein and Planar Cell Polarity (PCP) Pathway during Embryonic Development in Mice

Confronting the Need for Conceptual Change in Pre-Service Science Education

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