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Author Joann Trejo

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The α-arrestin ARRDC3 is an Emerging Multifunctional Adaptor Protein in Cancer.

Helen Wedegaertner, Wen-An Pan, Carlos C Gonzalez, David J Gonzalez, Joann Trejo,

<h4>Significance</h4>Adaptor proteins control the spatial and temporal dynamics of cellular signaling. Dysregulation of adaptor protein function can cause aberrant cell signaling and promote cancer. The arrestin adaptor proteins are known to regulate signaling by the superfamily of G protein-coupled receptors (GPCRs). GPCRs are highly druggable and implicated in cancer progression. ... Read more >>

Antioxid Redox Signal (Antioxidants & redox signaling)
[2021, :]

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Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption.

Cara C Rada, Hilda Mejia-Pena, Neil J Grimsey, Isabel Canto Cordova, Joshua Olson, Jacob M Wozniak, David J Gonzalez, Victor Nizet, JoAnn Trejo,

[Figure: see text]. ... Read more >>

Sci Signal (Science signaling)
[2021, 14(698):eabc1044]

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α-Arrestin ARRDC3 tumor suppressor function is linked to GPCR-induced TAZ activation and breast cancer metastasis.

Aleena K S Arakaki, Wen-An Pan, Helen Wedegaertner, Ivette Roca-Mercado, Logan Chinn, Taranjit S Gujral, JoAnn Trejo,

The α-arrestin domain containing protein 3 (ARRDC3) is a tumor suppressor in triple-negative breast carcinoma (TNBC), a highly metastatic subtype of breast cancer that lacks targeted therapies. Thus, understanding the mechanisms and targets of ARRDC3 in TNBC is important. ARRDC3 regulates trafficking of protease-activated receptor 1 (PAR1, also known as ... Read more >>

J Cell Sci (Journal of cell science)
[2021, 134(8):]

Cited: 1 time

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aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete β-arrestin-2 mediated SphK1-S1PR1-Akt signaling axis

Olivia Molinar-Inglis, Cierra Birch, Dequina Nicholas, Metzli Cisneros-Aguirre, Anand Patwardhan, Buxin Chen, Neil Grimsey, Patrick Gomez-Menzies, Huilan Lin, Luisa Coronel, Mark Lawson, Hemal Patel, JoAnn Trejo,

Endothelial dysfunction is associated with multiple vascular diseases and lacks effective treatments. Activated Protein C (aPC) is a promising biotherapeutic that signals via protease-activated receptor-1 (PAR1) to promote diverse cytoprotective responses, including endothelial barrier stabilization, anti-inflammatory and anti-apoptotic activities, which is facilitated by co-receptors. We showed that aPC-activated PAR1 signals ... Read more >>

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Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time.

Anand Patwardhan, Norton Cheng, JoAnn Trejo,

G protein-coupled receptors (GPCRs) are a large family comprising >800 signaling receptors that regulate numerous cellular and physiologic responses. GPCRs have been implicated in numerous diseases and represent the largest class of drug targets. Although advances in GPCR structure and pharmacology have improved drug discovery, the regulation of GPCR function ... Read more >>

Pharmacol Rev (Pharmacological reviews)
[2021, 73(1):120-151]

Cited: 9 times

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The burden of service for faculty of color to achieve diversity and inclusion: the minority tax.

JoAnn Trejo,

The exclusion of Blacks/African-Americans, Latinx/Hispanics, and Indigenous people from science has resulted in their underrepresentation in the biomedical workforce, especially in academia. Faculty diversity at academic institutions is unacceptably low (<6%) and has remained unchanged in the past 20 years. Despite low representation, faculty of color are disproportionately tasked with ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2020, 31(25):2752-2754]

Cited: 2 times

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Subcellular hot spots of GPCR signaling promote vascular inflammation.

Cierra A Birch, Olivia Molinar-Inglis, JoAnn Trejo,

G-coupled protein receptors (GPCRs) comprise the largest class of druggable targets. Signaling by GPCRs is initiated from subcellular hot spots including the plasma membrane, signalosomes, and endosomes to contribute to vascular inflammation. GPCR-G protein signaling at the plasma membrane causes endothelial barrier disruption and also cross-talks with growth factor receptors ... Read more >>

Curr Opin Endocr Metab Res (Current opinion in endocrine and metabolic research)
[2021, 16:37-42]

Cited: 6 times

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MON-009 GLUT1-Mediated Glycolysis Facilitates GnRH-Induced Secretion of Luteinizing Hormone

Dequina Nicholas, Vashti Knight, Karen Tonsfeldt, Tomohiro Terasaka, Olivia Molinar-Inglis, Shannon Brooke Zoe Stephens, Joann Trejo, Alexander S Kauffman, Pamela L Mellon, Mark A Lawson,

Abstract Reproduction requires intensive energy expenditure, and energy availability impacts the function of the reproductive endocrine HPG-axis. Accordingly, the reproductive axis is suppressed during hypoglycemia. Circulating blood glucose can directly interact with gonadotropes within the highly vascular pituitary. Therefore, it is possible that gonadotropes may sense energy availability via the ... Read more >>

J Endocr Soc (Journal of the Endocrine Society)
[2020, 4(Suppl 1):]

Cited: 0 times

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Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics.

Jeremiah Keyes, Ambhighainath Ganesan, Olivia Molinar-Inglis, Archer Hamidzadeh, Jinfan Zhang, Megan Ling, JoAnn Trejo, Andre Levchenko, Jin Zhang,

A variety of different signals induce specific responses through a common, extracellular-signal regulated kinase (ERK)-dependent cascade. It has been suggested that signaling specificity can be achieved through precise temporal regulation of ERK activity. Given the wide distrubtion of ERK susbtrates across different subcellular compartments, it is important to understand how ... Read more >>

Elife (eLife)
[2020, 9:]

Cited: 7 times

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Phosphoproteomic analysis of protease-activated receptor-1 biased signaling reveals unique modulators of endothelial barrier function.

Ying Lin, Jacob M Wozniak, Neil J Grimsey, Sravan Girada, Anand Patwardhan, Olivia Molinar-Inglis, Thomas H Smith, John D Lapek, David J Gonzalez, JoAnn Trejo,

Thrombin, a procoagulant protease, cleaves and activates protease-activated receptor-1 (PAR1) to promote inflammatory responses and endothelial dysfunction. In contrast, activated protein C (APC), an anticoagulant protease, activates PAR1 through a distinct cleavage site and promotes anti-inflammatory responses, prosurvival, and endothelial barrier stabilization. The distinct tethered ligands formed through cleavage of ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, 117(9):5039-5048]

Cited: 2 times

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Signaling Diversity Enabled by Rap1-Regulated Plasma Membrane ERK with Distinct Temporal Dynamics

Jeremiah Keyes, Ambhighainath Ganesan, Olivia Molinar-Inglis, Archer Hamidzadeh, Megan Ling, JoAnn Trejo, Andre Levchenko, Jin Zhang,

A variety of different signals induce specific responses through a common, ERK-dependent kinase cascade. It has been suggested that signaling specificity can be achieved through precise temporal regulation of ERK activity. Given the wide distrubtion of ERK susbtrates across different subcellular compartments, it is important to understand how ERK activity ... Read more >>

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A modular laboratory course using planarians to study genes involved in tissue regeneration.

Stacy D Ochoa, Michael R Dores, John M Allen, Tuan Tran, Maryan Osman, Nidia P Vázquez Castellanos, JoAnn Trejo, Ricardo M Zayas,

Undergraduate research experiences are excellent opportunities to engage students in science alongside experienced scientists, but at large institutions, it is challenging to accommodate all students. To address and engage a larger number of students, we developed a modular laboratory course based on the course-based undergraduate research experiences model. This new ... Read more >>

Biochem Mol Biol Educ (Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology)
[2019, 47(5):547-559]

Cited: 0 times

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G protein-coupled receptors activate p38 MAPK via a non-canonical TAB1-TAB2- and TAB1-TAB3-dependent pathway in endothelial cells.

Neil J Grimsey, Ying Lin, Rachan Narala, Cara C Rada, Hilda Mejia-Pena, JoAnn Trejo,

Endothelial dysfunction is induced by inflammatory mediators including multiple G protein-coupled receptor (GPCR) agonists. However, the GPCR signaling pathways that promote endothelial dysfunction are incompletely understood. We previously showed that thrombin promotes endothelial barrier disruption through autophosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) via a non-canonical transforming growth ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2019, 294(15):5867-5878]

Cited: 13 times

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Endo-lysosomal sorting of G-protein-coupled receptors by ubiquitin: Diverse pathways for G-protein-coupled receptor destruction and beyond.

Michael R Dores, JoAnn Trejo,

Ubiquitin is covalently attached to substrate proteins in the form of a single ubiquitin moiety or polyubiquitin chains and has been generally linked to protein degradation, however, distinct types of ubiquitin linkages are also used to control other critical cellular processes like cell signaling. Over forty mammalian G protein-coupled receptors ... Read more >>

Traffic (Traffic (Copenhagen, Denmark))
[2019, 20(2):101-109]

Cited: 12 times

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A Tyrosine Switch on NEDD4-2 E3 Ligase Transmits GPCR Inflammatory Signaling.

Neil J Grimsey, Rachan Narala, Cara C Rada, Sohum Mehta, Bryan S Stephens, Irina Kufareva, John Lapek, David J Gonzalez, Tracy M Handel, Jin Zhang, JoAnn Trejo,

Ubiquitination is essential for protein degradation and signaling and pivotal to many physiological processes. Ubiquitination of a subset of G-protein-coupled receptors (GPCRs) by the E3 ligase NEDD4-2 is required for p38 activation, but how GPCRs activate NEDD4-2 to promote ubiquitin-mediated signaling is not known. Here, we report that the GPCR ... Read more >>

Cell Rep (Cell reports)
[2018, 24(12):3312-3323.e5]

Cited: 13 times

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Faculty Equity, Diversity, Culture and Climate Change in Academic Medicine: A Longitudinal Study.

Deborah Wingard, JoAnn Trejo, Monica Gudea, Seneca Goodman, Vivian Reznik,

There is a national call for academic medicine to use evidence-based initiatives to improve its culture and climate. The authors report data-driven policy and programmatic interventions that were associated with increased faculty diversity, equity, respectful behavior and improved faculty climate, at UC San Diego Health Sciences.<h4>Methods</h4>Based on demographic and survey ... Read more >>

J Natl Med Assoc (Journal of the National Medical Association)
[2019, 111(1):46-53]

Cited: 6 times

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GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling.

Aleena K S Arakaki, Wen-An Pan, JoAnn Trejo,

G protein-coupled receptors (GPCRs) are a large diverse family of cell surface signaling receptors implicated in various types of cancers. Several studies indicate that GPCRs control many aspects of cancer progression including tumor growth, invasion, migration, survival and metastasis. While it is known that GPCR activity can be altered in ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2018, 19(7):]

Cited: 25 times

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The unfolded protein response regulator ATF6 promotes mesodermal differentiation.

Heike Kroeger, Neil Grimsey, Ryan Paxman, Wei-Chieh Chiang, Lars Plate, Ying Jones, Peter X Shaw, JoAnn Trejo, Stephen H Tsang, Evan Powers, Jeffery W Kelly, R Luke Wiseman, Jonathan H Lin,

ATF6 encodes a transcription factor that is anchored in the endoplasmic reticulum (ER) and activated during the unfolded protein response (UPR) to protect cells from ER stress. Deletion of the isoform activating transcription factor 6α (ATF6α) and its paralog ATF6β results in embryonic lethality and notochord dysgenesis in nonhuman vertebrates, ... Read more >>

Sci Signal (Science signaling)
[2018, 11(517):]

Cited: 22 times

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The α-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G protein-coupled receptor lysosomal sorting and signaling.

Aleena K S Arakaki, Wen-An Pan, Huilan Lin, JoAnn Trejo,

Aberrant G protein-coupled receptor (GPCR) expression and activation has been linked to tumor initiation, progression, invasion, and metastasis. However, compared with other cancer drivers, the exploitation of GPCRs as potential therapeutic targets has been largely ignored, despite the fact that GPCRs are highly druggable. Therefore, to advance the potential status ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2018, 293(9):3350-3362]

Cited: 13 times

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A reflection on faculty diversity in the 21st century.

JoAnn Trejo,

The 21st century is nearly two decades old, and the faculty ranks at our educational institutions remain sparsely diverse. While educational institutions are continually being challenged to increase the diversity of their faculty, progress is slow. This essay offers a perspective on the importance of diversity in our educational institutions ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2017, 28(22):2911-2914]

Cited: 1 time

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Protease-activated receptor-4 and purinergic receptor P2Y12 dimerize, co-internalize, and activate Akt signaling via endosomal recruitment of β-arrestin.

Thomas H Smith, Julia G Li, Michael R Dores, JoAnn Trejo,

Vascular inflammation and thrombosis require the concerted actions of several different agonists, many of which act on G protein-coupled receptors (GPCRs). GPCR dimerization is a well-established phenomenon that can alter protomer function. In platelets and other cell types, protease-activated receptor-4 (PAR4) has been shown to dimerize with the purinergic receptor ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2017, 292(33):13867-13878]

Cited: 14 times

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A general method for site specific fluorescent labeling of recombinant chemokines.

Tetsuya Kawamura, Bryan Stephens, Ling Qin, Xin Yin, Michael R Dores, Thomas H Smith, Neil Grimsey, Ruben Abagyan, Joann Trejo, Irina Kufareva, Mark M Fuster, Catherina L Salanga, Tracy M Handel,

Chemokines control cell migration in many contexts including development, homeostasis, immune surveillance and inflammation. They are also involved in a wide range of pathological conditions ranging from inflammatory diseases and cancer, to HIV. Chemokines function by interacting with two types of receptors: G protein-coupled receptors on the responding cells, which ... Read more >>

PLoS One (PloS one)
[2014, 9(1):e81454]

Cited: 12 times

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Challenges and Opportunities in Protease-Activated Receptor Drug Development.

Justin R Hamilton, JoAnn Trejo,

Protease-activated receptors (PARs) are a unique class of G protein-coupled receptors (GPCRs) that transduce cellular responses to extracellular proteases. PARs have important functions in the vasculature, inflammation, and cancer and are important drug targets. A unique feature of PARs is their irreversible proteolytic mechanism of activation that results in the ... Read more >>

Annu Rev Pharmacol Toxicol (Annual review of pharmacology and toxicology)
[2017, 57:349-373]

Cited: 26 times

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Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

Buxin Chen, David P Siderovski, Richard R Neubig, Mark A Lawson, Joann Trejo,

The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2014, 289(3):1580-1591]

Cited: 8 times

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Protease-activated Receptor-4 Signaling and Trafficking Is Regulated by the Clathrin Adaptor Protein Complex-2 Independent of β-Arrestins.

Thomas H Smith, Luisa J Coronel, Julia G Li, Michael R Dores, Marvin T Nieman, JoAnn Trejo,

Protease-activated receptor-4 (PAR4) is a G protein-coupled receptor (GPCR) for thrombin and is proteolytically activated, similar to the prototypical PAR1. Due to the irreversible activation of PAR1, receptor trafficking is intimately linked to signal regulation. However, unlike PAR1, the mechanisms that control PAR4 trafficking are not known. Here, we sought ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2016, 291(35):18453-18464]

Cited: 8 times

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