Age-related changes in lck-Vav signaling pathways in mouse CD4 T cells.
Activation of lck-fyn kinases during T cell receptor signaling leads to Vav phosphorylation, activation of downstream targets including Rac1, and a transient decline in ezrin and moesin phosphorylation. We have shown that age increases Rac1 activity and lowers ezrin and moesin phosphorylation in resting mouse CD4 cells, changes that could be the results of alterations in lck-Vav signaling. Analysis of Vav in CD4 cells from old mice shows increases in the phosphorylation of two key regulatory residues, Tyr160 and Tyr174, suggesting enhancement of Vav GTPase activity. In addition, analysis of lck status also shows age-related increases in phosphorylation of two key residues, Tyr394 and Tyr505, which have opposite effects on lck function. These changes in lck-Vav signals in resting CD4 cells may contribute in turn to age-related increases in Rac1 activity and declines in phosphorylation of cytoskeletal proteins including Ezrin and Moesin.
Garcia
Gonzalo G
GG
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48105, USA. gonzola@umich.edu
Miller
Richard A
RA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
D017252:CD3 Complex; C485468:Cd3e protein, mouse; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D009479:Neuropeptides; D051567:Proto-Oncogene Proteins c-vav; C484602:Rac1 protein, mouse; D014157:Transcription Factors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein