Activation of the Ancestral Polarity Regulator Protein Kinase C{zeta} at the Immunological Synapse Drives Polarization of Th Cell Secretory Machinery toward APCs.
Summary of "Activation of the Ancestral Polarity Regulator Protein Kinase C{zeta} at the Immunological Synapse Drives Polarization of Th Cell Secretory Machinery toward APCs."
A key feature in T lymphocyte biology is that Th cells rapidly polarize their secretory machinery toward cognate APCs. The molecular mechanisms of these dynamic Th cell responses and their impact on APC biology remain to be elucidated. In this study, we demonstrate that protein kinase Czeta (PKCzeta) is rapidly activated at the immunological synapse (IS) in human Th cells interacting with cognate dendritic cells (DCs) and that a functional PKCzeta is required for the polarization of Th cell secretory machinery toward DCs. We also show that PKCzeta-dependent Th cell polarization allows dedicated delivery of IFN-gamma and CD40L at the IS and is required for the activation of cognate DCs to IL-12 production. PKCzeta synaptic activation is a low-threshold phenomenon and, in Th cells interacting with multiple DCs, selectively occurs at the IS formed with the DCs offering the strongest stimulus leading to dedicated Th cell polarization. Our results identify the PKCzeta signaling pathway as a key component of the Th cell polarization machinery and provide a molecular basis for T cell-dedicated activation of cognate DCs.
Affiliation
Institut National de la Santé et de la Recherche Médicale, Unité 563, Section Dynamique Moléculaire des Interactions Lymphocytaires, Centre de Physiopathologie de Toulouse Purpan;
Journal Details
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20679531
- DOI: http://dx.doi.org/10.4049/jimmunol.1000739
Medical and Biotech [MESH] Definitions
Cyclic Amp-dependent Protein Kinase Riialpha Subunit
A type II cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a higher affinity for cAMP than that of the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIIBETA SUBUNIT. Binding of this subunit by A KINASE ANCHOR PROTEINS may play a role in the cellular localization of type II protein kinase A.
Cyclic Amp-dependent Protein Kinase Riibeta Subunit
A type II cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIIALPHA SUBUNIT. Binding of this subunit by A KINASE ANCHOR PROTEINS may play a role in the cellular localization of type II protein kinase A.
Elongation Factor 2 Kinase
A monomeric calcium-calmodulin-dependent protein kinase subtype that specifically phosphorylates PEPTIDE ELONGATION FACTOR 2. The enzyme lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE, however it is regulated by phosphorylation by PROTEIN KINASE A and through intramolecular autophosphorylation.
Calcium-calmodulin-dependent Protein Kinase Type 2
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Inhibitor Of Differentiation Protein 1
A negative regulator of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS that blocks activation of CYCLIN-DEPENDENT KINASE INHIBITOR P16 and is de-regulated in a variety of NEOPLASMS.
PubMed Articles
Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity.
Rho-associated kinase (Rho-kinase/ROCK/ROK) is an effector of the small GTPase Rho and belongs to the AGC family of kinases. Rho-kinase has pleiotropic functions including the regulation of cellular c...
Tagging the cell surface receptor with ubiquitin is believed to provide a signal for the endocytic pathway. E3 ubiquitin ligases such as Cbl-b and Itch have been implicated in T cell activation and to...
The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction.
The cell polarity regulator, human Scribble (hScrib), is a potential tumour suppressor whose loss is a frequent event in late-stage cancer development. Little is yet known about the mode of action of...
Recognition of gastric epithelial dysplasia, although a key to cancer prevention, can be challenging. In this study, we evaluated whether Lgl2 can serve as a marker of gastric foveolar-type dysplasia....
The activation strain model of chemical reactivity.
Herein, we provide an account of the activation strain model of chemical reactivity and its recent applications. In this model, the potential energy surface DeltaE(zeta) along the reaction coordinate...
Clinical Trials
Polarity Therapy for American Indian Caregivers of Dementia Patients
The purpose of this study is to assess the effectiveness of polarity therapy (PT), a complementary and alternative medicine treatment, in American Indian caregivers living in the Pacific N...
Molecular Markers of Human Sperm Function
Objectives: Male factor infertility is poorly understood and our ability to evaluate the male contribution to a couple's infertility is very limited. The overarching goal of this project...
Effects Of High Voltage Pulsed Current On Post-Traumatic Injuries
The investigators hypothesis is that HVPC with negative polarity diminishes local post-traumatic edema in ankle sprains. Therefore, the objective of this study was to analyze the effect of...
Defective Atypical Protein Kinase C (PKC) Activation in Diabetes and Metabolic Syndrome
The investigators are examining the activation of insulin signaling factors in skeletal muscles of human diabetics. The investigators are characterizing the defects in signaling, and are e...
Genetic Analysis of African-Americans With High Blood Pressure
The purpose of this study is to learn if kinase, a protein found in the heart, contributes to thickening of the heart muscle in people with high blood pressure. A protein called myosin ca...
