PI3K/AKT signaling and systemic autoimmunity.
The phosphoinositide 3-kinase (PI3K)/Akt signaling axis plays an important role in cellular proliferation and growth signaling. With respect to the immune system, a growing body of data is helping to elucidate the role of this pathway in lymphocyte development, as well as to show how perturbations that lead to unregulated activation in this pathway may produce systemic autoimmunity or malignancy. Various knockout and transgenic murine models have been described for key mediators of this signaling pathway. Many of these models resulting in the activation of this pathway demonstrate features of systemic autoimmunity, linking this pathway to autoimmune disease. Here, we review recently described murine models that exhibit activated PI3K/Akt signaling and the potential role this pathway in autoimmune disease, and also discuss the therapeutic implications of these findings.
Patel
Rahul K
RK
Department of Rheumatology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390-8884, USA.
Mohan
Chandra
C
D000818:Animals; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D051379:Mice; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; C494918:AKT1 protein, human; C487757:Pten protein, mouse