Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1.
Leukocyte functional antigen 1 (LFA-1), with intercellular adhesion molecule ligands, mediates T cell adhesion, but the signaling pathways and functional effects imparted by LFA-1 are unclear. Here, intracellular phosphoprotein staining with 13-dimensional flow cytometry showed that LFA-1 activation induced phosphorylation of the beta(2) integrin chain and release of Jun-activating binding protein 1 (JAB-1), and mediated signaling of kinase Erk1/2 through cytohesin-1. Dominant negatives of both JAB-1 and cytohesin-1 inhibited interleukin 2 production and impaired T helper type 1 differentiation. LFA-1 stimulation lowered the threshold of T cell activation. Thus, LFA-1 signaling contributes to T cell activation and effects T cell differentiation.
Perez
Omar D
OD
Department of Microbiology and Immunology, and The Baxter Laboratory of Genetic Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.
Mitchell
Dennis
D
Jager
Gina C
GC
South
Sharon
S
Murriel
Chris
C
McBride
Jacqueline
J
Herzenberg
Lee A
LA
Kinoshita
Shigemi
S
Nolan
Garry P
GP
D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010447:Peptide Hydrolases; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C065289:ICAM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D014157:Transcription Factors; C100723:cytohesin-1; D012694:Serine; D020928:Mitogen-Activated Protein Kinases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex