Akt1 plays a key role in regulating cell survival, insulin signaling, angiogenesis… and, in some cases, tumor formation. Activation of the PI3K pathway may result in the recruitment of Akt1 to the plasma membrane via the pleckstrin homology domain (PH) of the kinase. Akt1 fully activated by phosphorylation at Ser308 (by PDK1) and Thr478 (by mTOR and DNA-PK) can itself phosphorylate a wide range of substrates including transcription factors, kinases and other proteins with important signaling.
Akt1 mutations have been associated with breast, colorectal and ovarian cancer. Mutations have also been found in urinary tract, thyroid, endometrial and prostate cancers.
More than 99% of somatic mutations are substitutions. Most mutations are found in the first 50 amino acids (PH domain), with a mutation “hotspot” at amino acid 17.
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