Activation of the PKB/AKT Pathway by ICAM-2

We identified intracellular adhesion molecule-2 (ICAM-2) in a genetic screen as an activator of the PI3K/AKT pathway leading to inhibition of apoptosis. ICAM-2 induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation, resulting in phosphatidylinositol 3,4,5 production, PDK-1...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2002, Vol.16 (1), p.51-65
Main Authors: Perez, Omar D, Kinoshita, Shigemi, Hitoshi, Yasumichi, Payan, Donald G, Kitamura, Toshio, Nolan, Garry P, Lorens, James B
Format: Article
Language:English
Subjects:
3-Phosphoinositide-Dependent Protein Kinases
3T3 Cells
Actinin - metabolism
Animals
Antigens, CD - physiology
Apoptosis
Binding Sites
CD19 antigen
CD4 antigen
Cell Adhesion Molecules - physiology
Cell culture
Cell Survival
Cloning
Cytoskeletal Proteins
Enzyme Activation
Experiments
Fas antigen
Flow cytometry
Gene expression
Genotype & phenotype
intercellular adhesion molecule 2
Kinases
Leukemia
Lymphocytes
Mice
Phosphatidylinositol 3-Kinases - metabolism
Phosphoproteins - metabolism
Phosphorylation
Protein-Serine-Threonine Kinases - metabolism
Proteins
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Retroviridae - genetics
Signal Transduction
Tumor Necrosis Factor-alpha - pharmacology
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Summary:We identified intracellular adhesion molecule-2 (ICAM-2) in a genetic screen as an activator of the PI3K/AKT pathway leading to inhibition of apoptosis. ICAM-2 induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation, resulting in phosphatidylinositol 3,4,5 production, PDK-1 and AKT activation, and subsequent phosphorylation of AKT targets BAD, GSK3, and FKHR. ICAM-2 clustering protected primary human CD19 + cells from TNFα- and Fas-mediated apoptosis as determined by single-cell analysis. ICAM-2 engagement by CD19 + cells of its natural receptor, LFA-1, on CD4 + naive cells specifically induced AKT activity in the absence of an MHC-peptide interaction. These results attribute a novel signaling function to ICAM-2 that might suggest mechanisms by which ICAM-2 signals intracellular communication at various immunological synapses.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(02)00266-2