A Single PDZ Domain Protein Interacts with the Menkes Copper ATPase, ATP7A

Stephenson, Sarah E. M.; Dubach, Daphne; Lim, Chris; Mercer, Julian F. B.; Fontaine, Sharon La

doi:10.1074/jbc.m505889200

Cited by 32 publications

(42 citation statements)

References 64 publications

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“…Among the novel candidate effectors, PISP/PDZK11, a protein with a single PDZ domain, showed the highest fold activation and similar kinetics as IRS-1. PDZK11 has been described as an interactor of the plasma membrane Ca 2ϩ -ATPase (PMCA) and as an interactor for the Menkes copper ATPase (AIPP1) (36). The dramatic increase in tyrosine phosphorylation of PDZK11 after insulin treatment strongly suggests its involvement in calcium signaling as part of the insulin cascade.…”

Section: Discussionmentioning

confidence: 98%

Dissection of the insulin signaling pathway via quantitative phosphoproteomics

Krüger

Kratchmarova

Blagoev

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

254

208

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The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC) in differentiated brown adipocytes. Of 40 identified insulininduced effectors, 7 have not previously been described in insulin signaling, including SDR, PKC␦ binding protein, LRP-6, and PISP/ PDZK11, a potential calcium ATPase binding protein. A proteomic interaction screen with PISP/PDZK11 identified the calcium transporting ATPase SERCA2, supporting a connection to calcium signaling. The combination of quantitative phosphoproteomics with cell culture models provides a powerful strategy to dissect the insulin signaling pathways in intact cells.diabetes ͉ insulin action ͉ tyrosine phosphorylation R eversible phosphorylation is a major regulatory mechanism controlling the activity of proteins. Many signaling pathways, including the insulin/IGF-1 signaling pathway, transduce signals from the cell surface to downstream targets via tyrosine kinases and phosphatases (1). Insulin or IGF-1 binding initiates a complex cascade of events, starting with phosphorylation of specific tyrosine residues on the insulin and the IGF-1 receptors (2). Once activated, these receptors phosphorylate a number of docking proteins; the best characterized are the insulin receptor substrate (IRS) proteins 1-4 (3). IRS 1-4 interact with other intracellular signaling molecules primarily through SH2 domains leading to activation of several downstream pathways. These in turn coordinate and regulate vesicle trafficking, protein synthesis, and glucose uptake. The insulin receptor and its substrates, therefore, constitute the first critical node in the insulin signaling network (1) and thus define the full set of proteins that are tyrosine phosphorylated upon insulin stimulation and provide information that is central to determining the molecules involved in this signaling network.Mass spectrometry (MS)-based proteomics has become increasingly powerful not only to identify complex protein mixtures but also regulated protein modifications (4). We have studied tyrosine phosphorylated effectors and interactors in the EGF pathway (5, 6) and others have used MS to study tyrosine phosphorylation of the insulin pathway in white adipocytes (7). To quantify the time course of stimulation, we employ stable isotope labeling with amino acids in cell culture (SILAC) (8). Labeling three cell states by SILAC allows measuring a time course of activation of tyrosine phosphorylation by quantifying the relative protein amounts after antiphosphotyrosine immunoprecipitation. Here, we quanti...

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Section: Discussionmentioning

confidence: 98%

Dissection of the insulin signaling pathway via quantitative phosphoproteomics

Krüger

Kratchmarova

Blagoev

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

254

208

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“…Several proteins involved in specific interactions with ATP7A and ATP7B have been identified (12,(49)(50)(51)93). However, the contribution of these proteins to the exit of ATP7A and ATP7B from the TGN, to the retention in the vesicles, endocytosis, and the return of CuATPases to the TGN remains unknown.…”

Section: Mechanisms That Control Intracellular Distribution Of Cu-atpmentioning

confidence: 99%

Biochemical basis of regulation of human copper-transporting ATPases

Lutsenko

LeShane

Shinde

2007

Archives of Biochemistry and Biophysics

122

115

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SummaryCopper is essential for cell metabolism as a cofactor of key metabolic enzymes. The biosynthetic incorporation of copper into secreted and plasma membrane-bound proteins requires activity of the copper-transporting ATPases (Cu-ATPases) ATP7A and ATP7B. The Cu-ATPases also export excess copper from the cell and thus critically contribute to the homeostatic control of copper. The trafficking of Cu-ATPases from the trans-Golgi network to endocytic vesicles in response to various signals allows for the balance between the biosynthetic and copper exporting functions of these transporters. Although significant progress has been made towards understanding the biochemical characteristics of human Cu-ATPase, the mechanisms that control their function and intracellular localization remain poorly understood. In this review, we summarize current information on structural features and functional properties of ATP7A and ATP7B. We also describe sequence motifs unique for each Cu-ATPase and speculate about their role in regulating ATP7A and ATP7B activity and trafficking.

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“…7) or as ATPase-interacting PDZ protein (AIPP1; Ref. 21), is a ubiquitously expressed small protein that has been recently shown to interact with other membrane transporters and influence their activity [e.g., Ca-ATPase and Menkes copper ATPase (ATP7A); Refs. 7,21].…”

mentioning

confidence: 99%

Association of PDZ-containing protein PDZD11 with the human sodium-dependent multivitamin transporter

Nabokina

Subramanian

Said

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Nabokina SM, Subramanian VS, Said HM. Association of PDZcontaining protein PDZD11 with the human sodium-dependent multivitamin transporter. Am J Physiol Gastrointest Liver Physiol 300: G561-G567, 2011. First published December 23, 2010 doi:10.1152/ajpgi.00530.2010Intestinal absorption of biotin is mediated via the sodium-dependent multivitamin transporter (SMVT). Studies from our laboratory and others have characterized different aspects of the human SMVT (hSMVT), but nothing is currently known about protein(s) that may interact with hSMVT and affect its physiology/biology. In this study, a PDZ-containing protein PDZD11 was identified as an interacting partner with hSMVT using yeast two-hybrid screen of a human intestinal cDNA library. The interaction between hSMVT and PDZD11 was confirmed by in vitro GST-pull-down assay and in vivo in a mammalian cell environment by a two-hybrid luciferase and coimmunoprecipitation assays. Furthermore, confocal imaging of live human intestinal epithelial HuTu-80 cells expressing hSMVT-GFP and DsRed-PDZD11 demonstrated colocalization of these two proteins. We also examined the functional consequence of the interaction between hSMVT and PDZD11 in HuTu-80 cells and observed significant induction in [ 3 H]biotin uptake upon coexpression of hSMVT and PDZD11. In contrast, knocking down of PDZD11 with genespecific small interfering RNA led to a significant decrease in biotin uptake; biotinylation assay showed this to be associated with a marked decrease in level of expression of hSMVT at the cell membrane. By truncation approach, we also demonstrated that the PDZ binding domain that is located in the COOH-terminal tail of hSMVT polypeptide is involved in the interaction with PDZD11. These results demonstrate for the first time that PDZD11 is an interacting partner with hSMVT in intestinal epithelial cells and that this interaction affects hSMVT function and cell biology. biotin transport; protein-protein interactions; yeast two-hybrid analysis

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A Single PDZ Domain Protein Interacts with the Menkes Copper ATPase, ATP7A

Cited by 32 publications

References 64 publications

Dissection of the insulin signaling pathway via quantitative phosphoproteomics

Dissection of the insulin signaling pathway via quantitative phosphoproteomics

Biochemical basis of regulation of human copper-transporting ATPases

Association of PDZ-containing protein PDZD11 with the human sodium-dependent multivitamin transporter

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