Alteration in protein kinase B (AKT) activity in platelets from patients with systemic sclerosis.
We have previously reported that there is an increase in phosphotidylinositide-3 kinase activity secondary to increase in nitrotyrosylation in platelets from patients with SSc. Protein kinase B (Akt) is recruited to the plasma membrane by PI 3-K metabolites. Both enzymes play critical roles in signal transduction and activation of platelets. In the present investigation, we have studied the effect of postranslational modification of the activity of Akt. We have examined eight patients and eight controls and obtained results showing that enzymatic activity of Akt is increased in lysates of platelets from patients with SSc compared to normal volunteer controls. We have obtained results showing that there is no correlation of nitrotyrosylation of Akt on its enzymatic activity although Western blots show the enzyme has increased nitrotyrosylation. These results suggest that post-translational modification by nitrotyrosylation does not control Akt in SSc platelets. We concluded that the enhanced activity of PI 3-K and Akt in platelets from patients with SSc is mediated by different mechanisms.
Chiang
Thomas M
TM
Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA. tchiang@utmen.edu
Postlethwaite
Arnold E
AE
D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008954:Models, Biological; D009584:Nitrogen / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015539:Platelet Activation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000175:diagnosis* / Q000473:pathology*; D015398:Signal Transduction; D014443:Tyrosine / Q000737:chemistry
D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D009584:Nitrogen