Impaired CD45-associated tyrosine phosphatase activity during HIV-1 infection: implications for CD3 and CD4 receptor signalling.
Proper function of the protein tyrosine phosphatase CD45 is required for the positive regulation of the activity of src tyrosine kinases p56lck and p59fyn which participate in T-cell receptor and CD4 receptor signalling. In this study, the effect of HIV-1 infection on the function of CD45-associated tyrosine phosphatase activity in the H9 T-cell line has been investigated with respect to CD3 and CD4 ligation. A significant reduction in CD45-associated phosphatase activity was observed following CD3 + CD4 ligation in virally infected cells, whereas CD45 activity was not compromised following CD3 receptor ligation. Dysfunctional CD45 activity in infected cells was not attributable to reduced receptor surface expression induced by HIV-1, since CD4, CD3 and CD45 expression levels were found to be intact. Defective CD45 activity correlated with inhibted downstream signalling events as evidenced by reduced CD4-associated tyrosine kinase activity and inhibition of PLC-gamma1. Impaired CD45 function is likely to play a critical role in the inhibition of CD3/CD4 signalling thereby contributing to HIV-1 pathogenesis.
Guntermann
C
C
Department of Immunology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, EC1A 7BE, United Kingdom. christine_guntermann@macmailgw.dfci.harvard.edu
Amft
N
N
Murphy
B J
BJ
Nye
K E
KE
D000595:Amino Acid Sequence; D017252:CD3 Complex / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D016895:Culture Media, Serum-Free; D005755:Gastrins / Q000737:chemistry / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000502:physiology*; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D013379:Substrate Specificity
D017252:CD3 Complex; D015704:CD4 Antigens; D016895:Culture Media, Serum-Free; D005755:Gastrins; D016655:HIV Core Protein p24; C013550:gastrin 17; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases