Spatiotemporal control of cyclic AMP immunomodulation through the PKA-Csk inhibitory pathway is achieved by anchoring to an Ezrin-EBP50-PAG scaffold in effector T cells

Isabelle Cornez; Kjetil Taskén

doi:10.1016/j.febslet.2010.04.056

Spatiotemporal control of cyclic AMP immunomodulation through the PKA-Csk inhibitory pathway is achieved by anchoring to an Ezrin-EBP50-PAG scaffold in effector T cells

FEBS Lett. 2010 Jun 18;584(12):2681-8. doi: 10.1016/j.febslet.2010.04.056. Epub 2010 Apr 24.

Authors

Isabelle Cornez¹, Kjetil Taskén

Affiliation

¹ The Biotechnology Centre of Oslo, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway.

PMID: 20420835
DOI: 10.1016/j.febslet.2010.04.056

Abstract

A variety of immunoregulatory signals to effector T cells from monocytes, macrophages and regulatory T cells act through cyclic adenosine monophosphate. In the effector T cell, the protein kinase A (PKA) type I isoenzyme localizes to lipid rafts during T cell activation and modulates directly the proximal events that take place after engagement of the T cell receptor. The most proximal target for PKA phosphorylation is C-terminal Src kinase (Csk), which initiates a negative signal pathway that fine-tunes the T cell activation process. The A kinase anchoring protein Ezrin colocalizes PKA and Csk by forming a supramolecular signaling complex consisting of PKA, Ezrin, Ezrin/radixin/moesin (ERM) binding protein of 50 kDa (EBP50), phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (GEMs) (PAG) and Csk.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Animals
Cyclic AMP / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism
Cytoskeletal Proteins / metabolism
Humans
Lymphocyte Activation
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
Membrane Microdomains / metabolism
Membrane Proteins / metabolism
Models, Immunological
Phosphoproteins / metabolism
Signal Transduction / immunology
Sodium-Hydrogen Exchangers / metabolism
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism*
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / metabolism
src-Family Kinases / metabolism

Substances

Adaptor Proteins, Signal Transducing
Cytoskeletal Proteins
Membrane Proteins
PAG1 protein, human
Phosphoproteins
Sodium-Hydrogen Exchangers
ezrin
sodium-hydrogen exchanger regulatory factor
Cyclic AMP
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
src-Family Kinases
Cyclic AMP-Dependent Protein Kinases