Protein Kinase Cα Promotes Cell Migration through a PDZ-Dependent Interaction with its Novel Substrate Discs Large Homolog 1 (DLG1)

O’Neill, Alan M.; Gallegos, Lisa L.; Justilien, Verline; Garcia, Erin L.; Leitges, Michael; Fields, Alan P.; Hall, Randy A.; Newton, Alexandra C.

doi:10.1074/jbc.m111.294603

Cited by 56 publications

(58 citation statements)

References 55 publications

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“…PKC exerts an important effect on antiapoptosis and metastasis of NSCLC cells. Metastasis of NSCLC cells can be stimulated by the activation of PKC through a C-terminal class I PDZ-dependent interaction with its substrate, discs large homology-1 [291]. In addition, an increase in the activity of PKC and nuclear PKC has been detected in lung metastatic nodules originating from other cancers such as HCC [292].…”

Section: Small and Nonsmall Cell Lung Carcinomamentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

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Section: Small and Nonsmall Cell Lung Carcinomamentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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“…PICK1 targets activated PKC␣ to synapses to phosphorylate the glutamate receptor subunit GluR2, leading to its endocytosis (77), but it can also act as a barrier to phosphorylation of the metabotropic glutamate receptor mGluR7a by PKC␣ (78). More recently, a family of Discs large homolog scaffolds that interact with the PDZ ligand of PKC␣ to facilitate cellular migration was also identified (79).…”

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confidence: 99%

Spatiotemporal Dynamics of Phosphorylation in Lipid Second Messenger Signaling

Antal

Newton

2013

Molecular & Cellular Proteomics

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The plasma membrane serves as a dynamic interface that relays information received at the cell surface into the cell. Lipid second messengers coordinate signaling on this platform by recruiting and activating kinases and phosphatases. Specifically, diacylglycerol and phosphatidylinositol 3,4,5-trisphosphate activate protein kinase C and Akt, respectively, which then phosphorylate target proteins to transduce downstream signaling. This review addresses how the spatiotemporal dynamics of protein kinase C and Akt signaling can be monitored using genetically encoded reporters and provides information on how the coordination of signaling at protein scaffolds or membrane microdomains affords fidelity and specificity in phosphorylation events. Molecular & Cellular Proteomics 12: 10.1074/mcp.R113.029819, 3498-3508, 2013.The alteration of protein or lipid structure by phosphorylation is one of the most effective ways to transduce extracellular signals into cellular actions. Phosphorylation can alter enzyme activity, regulate protein stability, affect protein interactions or localization, or influence other post-translational modifications. A plethora of cellular processes, including cell growth, differentiation, and migration, are tightly regulated by phosphorylation. Cellular homeostasis is achieved by means of a precisely regulated balance between phosphorylation and dephosphorylation, and disruption of this balance results in pathophysiologies. Kinases and phosphatases are antagonizing effector enzymes that respond to second messengers and mediate phosphorylation/dephosphorylation events.Two prominent lipid second messenger pathways are those mediated by diacylglycerol (DAG) 1 and phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) (Fig. 1A). These membrane-embedded second messengers recruit effector kinases containing specific membrane-targeting modules to membranes, thus activating them. Specifically, DAG recruits C1-domaincontaining proteins, notably protein kinase C (PKC), whereas PIP 3 recruits pleckstrin homology (PH) domain-containing proteins, such as Akt. Specificity and fidelity in signaling are often achieved via the compartmentalization of signaling on protein scaffolds and membrane microdomains, which can control the access of enzymes to particular substrates. In this review, we provide a brief background of the DAG and PIP 3 pathways and their effector kinases, PKC and Akt, respectively. We discuss sensors that have been developed to measure lipid second messenger levels and kinase activity at various subcellular compartments, the role of scaffolds and membrane microdomains in compartmentalizing signaling, and the consequences of dysregulation of second messenger signaling in disease. Lipid Second Messengers-Lipid second messengers are signaling molecules produced in response to extracellular stimuli. Targeting enzymes and their substrates to the same membrane constrains them to a space of reduced dimensionality, thus increasing the apparent concentration of the signaling complex and the likelihood and amp...

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“…In the same study, it was also shown that keratinocytes with silenced EPB41 exhibit reduced adhesion, cell spreading, migration, and motility. In addition, DLG1 has a role in wound healing, and it is proposed that the transglutaminase EPB41 binds to DLG1 (82). Ankyrin 1 could play a role in wound healing by initiating endothelial cell proliferation and/or adhesion via its interaction with CD44v10 and IP3 receptors on endothelial cell lipid rafts (83).…”

Section: Discussionmentioning

confidence: 99%

Mapping the Extracellular and Membrane Proteome Associated with the Vasculature and the Stroma in the Embryo

Soulet

Kilarski

Roux‐Dalvai

et al. 2013

Molecular & Cellular Proteomics

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In order to map the extracellular or membrane proteome associated with the vasculature and the stroma in an embryonic organism in vivo, we developed a biotinylation technique for chicken embryo and combined it with mass spectrometry and bioinformatic analysis. We also applied this procedure to implanted tumors growing on the chorioallantoic membrane or after the induction of granulation tissue. Membrane and extracellular matrix proteins were the most abundant components identified. Relative quantitative analysis revealed differential protein expression patterns in several tissues. Through a bioinformatic approach, we determined endothelial cell protein expression signatures, which allowed us to identify several proteins not yet reported to be associated with endothelial cells or the vasculature. This is the first study reported so far that applies in vivo biotinylation, in combination with robust label-free quantitative proteomics approaches and bioinformatic analysis, to an embryonic organism. It also provides the first description of the vascular and matrix proteome of the embryo that might constitute the starting point for further developments. Molecular & Cellular Proteomics 12:

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Protein Kinase Cα Promotes Cell Migration through a PDZ-Dependent Interaction with its Novel Substrate Discs Large Homolog 1 (DLG1)

Cited by 56 publications

References 55 publications

Protein Kinase C (PKC) Isozymes and Cancer

Protein Kinase C (PKC) Isozymes and Cancer

Spatiotemporal Dynamics of Phosphorylation in Lipid Second Messenger Signaling

Mapping the Extracellular and Membrane Proteome Associated with the Vasculature and the Stroma in the Embryo

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