Regulation of the Phosphoinositide Code by Phosphorylation of Membrane Readers

Troy A. Kervin; Michael Overduin

doi:10.3390/cells10051205

Regulation of the Phosphoinositide Code by Phosphorylation of Membrane Readers

Cells ◽

10.3390/cells10051205 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1205

Author(s):

Troy A. Kervin ◽

Michael Overduin

Keyword(s):

Nucleic Acids ◽

Genetic Code ◽

Protein Kinases ◽

Critical Role ◽

Protein Structures ◽

High Fidelity ◽

Selective Targeting ◽

Phosphatidylinositol Phosphates ◽

Phox Homology

The genetic code that dictates how nucleic acids are translated into proteins is well known, however, the code through which proteins recognize membranes remains mysterious. In eukaryotes, this code is mediated by hundreds of membrane readers that recognize unique phosphatidylinositol phosphates (PIPs), which demark organelles to initiate localized trafficking and signaling events. The only superfamily which specifically detects all seven PIPs are the Phox homology (PX) domains. Here, we reveal that throughout evolution, these readers are universally regulated by the phosphorylation of their PIP binding surfaces based on our analysis of existing and modelled protein structures and phosphoproteomic databases. These PIP-stops control the selective targeting of proteins to organelles and are shown to be key determinants of high-fidelity PIP recognition. The protein kinases responsible include prominent cancer targets, underscoring the critical role of regulated membrane readership.

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Critical role of nuclear factor‐κB and stress‐activated protein kinases in steroid unresponsiveness

The FASEB Journal ◽

10.1096/fj.02-0223fje ◽

2002 ◽

Vol 16 (13) ◽

pp. 1-19 ◽

Cited By ~ 70

Author(s):

Heike Bantel ◽

M. Lienhard Schmitz ◽

Armin Raible ◽

Michael Gregor ◽

Klaus Schulze‐Osthoff

Keyword(s):

Protein Kinases ◽

Critical Role ◽

Nuclear Factor Κb ◽

Nuclear Factor

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A Lys49 PhospholipaseA2, Isolated fromBothrops asperSnake Venom, Induces Lipid Droplet Formation in Macrophages Which Depends on Distinct Signaling Pathways and the C-Terminal Region

BioMed Research International ◽

10.1155/2013/807982 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 6

Author(s):

Karina Cristina Giannotti ◽

Elbio Leiguez ◽

Vanessa Moreira ◽

Neide Galvão Nascimento ◽

Bruno Lomonte ◽

...

Keyword(s):

Signaling Pathways ◽

Protein Kinases ◽

Inflammatory Responses ◽

Critical Role ◽

Terminal Sequence ◽

Pharmacological Interventions ◽

C Terminus ◽

Inflammatory Mechanism ◽

Terminal Loop

MT-II, a Lys49PLA2homologue devoid of catalytic activity fromB. aspervenom, stimulates inflammatory events in macrophages. We investigated the ability of MT-II to induce formation of lipid droplets (LDs), key elements of inflammatory responses, in isolated macrophages and participation of protein kinases and intracellular PLA2s in this effect. Influence of MT-II on PLIN2 recruitment and expression was assessed, and the effects of some synthetic peptides on LD formation were further evaluated. At noncytotoxic concentrations, MT-II directly activated macrophages to form LDs. This effect was reproduced by a synthetic peptide corresponding to the C-terminal sequence 115–129 of MT-II, evidencing the critical role of C-terminus for MT-II-induced effect. Moreover, MT-II induced expression and recruitment of PLIN2. Pharmacological interventions with specific inhibitors showed that PKC, PI3K, ERK1/2, and iPLA2, but notP38MAPKor cPLA2, signaling pathways are involved in LD formation induced by MT-II. This sPLA2homologue also induced synthesis of PGE2that colocalized to LDs. In conclusion, MT-II is able to induce formation of LDs committed to PGE2formation in a process dependent on C-terminal loop engagement and regulated by distinct protein kinases and iPLA2. LDs may constitute an important inflammatory mechanism triggered by MT-II in macrophages.

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Biochemical control systems operating in the early hours of germination

Canadian Journal of Botany ◽

10.1139/b83-406 ◽

1983 ◽

Vol 61 (12) ◽

pp. 3568-3577 ◽

Cited By ~ 65

Author(s):

Daphne J. Osborne

Keyword(s):

Dna Repair ◽

Nucleic Acids ◽

Control Systems ◽

Critical Role ◽

Genetic Integrity ◽

Biochemical Control

This review describes very early biochemical events during imbibition in seeds. It considers the control systems that regulate the production of nucleic acids and proteins when the dry seed first imbibes water. During the ageing of embryos in the dry state, DNA is progressively fragmented with an accumulation of single-stranded breaks. The critical role of DNA repair early in imbibition is considered in the context of genetic integrity of the nuclear template and successful germination.

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Does Interleukin-6 Bridge SARS-CoV-2 With Virus-Associated Cancers?

Journal of Immunotherapy and Precision Oncology ◽

10.36401/jipo-20-27 ◽

2021 ◽

Author(s):

Aldo Venuti ◽

Sara Donzelli ◽

Paola Nisticò ◽

Giovanni Blandino ◽

Gennaro Ciliberto

Keyword(s):

Interleukin 6 ◽

Viral Infections ◽

Critical Role ◽

Direct Interaction ◽

Molecular Profile ◽

Populations At Risk ◽

Selective Targeting ◽

B Virus ◽

Immunodeficiency Virus

ABSTRACT To date SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a member of the Coronaviridae family, has infected more than 40 million people worldwide. A second wave of SARS-CoV-2 infection is aggressively surging. The clinical worsening of SARS-CoV-2 infection appears to be strictly associated with comorbidities, which can be used to establish an intrinsic patient network whose molecular profile is pivotal for identifying and successfully treating populations at risk. Herein, we focus on the direct interaction between SARS-CoV-2 and virus-associated cancers, exploring the critical role of interleukin-6 (IL-6) as a mediator of this complex cross talk. IL-6 production is enhanced in diverse viral infections ranging from human papilloma virus (HPV) to hepatitis B virus (HBV), human immunodeficiency virus (HIV), and SARS-CoV-2 infection. High systemic levels of IL-6 are associated with viral persistence and poor clinical outcomes in SARS-CoV-2–infected patients. Blockade of IL-6/IL-6R, using specific molecules, is under investigation in active clinical trials for the treatment of patients with SARS-CoV-2. Although the data are as yet inconclusive, they pave the way for selective targeting of crucial cytokine-activated aberrant signaling in SARS-CoV-2 infection.

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The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

Perspectives on Language Learning and Education ◽

10.1044/lle15.2.50 ◽

2008 ◽

Vol 15 (2) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Amy Philofsky

Keyword(s):

Language Development ◽

Critical Role ◽

Children With Autism ◽

Autism Spectrum ◽

Children With Asd ◽

Prevalence Estimates ◽

Notable Increase ◽

Screening Assessment ◽

Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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