Akt1 is one of three isoforms of Akt belonging to the AGC family of serine/threonine kinases (Akt1, Akt2, and Akt3). All Akt isoforms contain an N-terminal Plekstrin Homology (PH) domain, a C-terminal regulatory domain, and a central catalytic kinase domain (1). Akt is a major downstream target of the PI3-K signaling pathway. The Akt1 isoform is fully activated by phosphorylation at three sites- T308, T450, and S473. Akt1 resides in an inactive state due to intramolecular interactions between the PH domain and the kinase domain. PI3-K signaling induces a conformational change that exposes the active sites to allow phosphorylation and activation of Akt1 (1). Akt plays a variety of roles in normal cellular metabolism, growth, proliferation, and survival. It has also been implicated in malignancies as a driver of angiogenesis, migration, and invasion. Recent studies have begun to tease apart the signaling specificity of the three Akt isoforms. Akt1 is expressed in many tissues and is specifically implicated in cell growth and survival (2). In contrast, Akt2 and Akt3 have more restricted expression patterns. The Akt pathway is a common survival pathway utilized by cancer cells; however, mutations in Akt itself are rare. Thus, dysregulation of Akt signaling in cancer is typically due to an alteration in upstream regulators of Akt. Given the extremely high prevalence of Akt activation in malignancies, Akt inhibition has been identified as a promising cancer therapeutic.
Akt1 antibodies can be used to look at total protein levels as well as phosphorylated/active protein levels. Sagatys et. al. sought to understand the role of Akt in the progression of esophageal adenocarcinoma (3). The group used a phospho-Akt antibody to assess Akt activation in 50 patient samples. Then the group used the Akt1 antibody to assess total Akt levels in the tissues. Using the Akt antibodies, the group found similar levels of total Akt1 but variable levels of phospho-Akt among their tissues samples. Matching the levels of Akt activation to tumor grade allowed the group to make a strong positive correlation between Akt activation and tumor progression. This identified Akt activation as a poor prognostic factor and warranted further investigation of Akt as a therapeutic target.
Akt inhibition has shown promising results as a novel cancer therapeutic. Nair et. al. studied the naturally occurring compound deguelin and its role as an Akt inhibitor (4). The group hypothesized that deguelin acted through suppression of the NFκB pathway. Through their investigation, they found that deguelin blocked Akt activation by TNF. The group used the anti-phospho Akt 1/2 antibody to look at levels of Akt activation in the presence of TNF stimulation with deguelin treatment. To ensure that each sample had the same level of Akt expression, the group used the total Akt antibody. The results showed almost complete inhibition of Akt phosphorylation in the presence of 10 µM deguelin. The group elucidated a complex mechanism by which deguelin inhibited NFκB activity to exert its antiproliferative and proapoptotic effects.
Novus Biologicals offers Akt1 reagents for your research needs including:
PMIDs:
