Feb 9, 2019.

Contents • • • • • • • • • • • • • • • • • • • • • • Family members - Isoforms [ ] is involved in cellular survival pathways, by inhibiting processes. Akt1 is also able to induce pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy, and general tissue growth. Mouse model with complete deletion of Akt1 manifests growth retardation and increased spontaneous apoptosis in tissues such as testes and thymus. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer. Akt (now also called Akt1) was originally identified as the in the transforming, AKT8.

Is an important signaling molecule in the. It is required to induce glucose transport. In a mouse which is null for Akt1 but normal for Akt2, glucose homeostasis is unperturbed, but the animals are smaller, consistent with a role for Akt1 in growth. In contrast, mice which do not have Akt2, but have normal Akt1, have mild growth deficiency and display a phenotype (), again consistent with the idea that Akt2 is more specific for the signaling pathway. Akt isoforms are overexpressed in a variety of human tumors, and, at the genomic level, are amplified in gastric adenocarcinomas (Akt1), ovarian (Akt2), pancreatic (Akt2) and breast (Akt2) cancer.

The role of is less clear, though it appears to be predominantly expressed in the brain. It has been reported that mice lacking Akt3 have small brains.

Name [ ] The name Akt does not refer to its function. The 'Ak' in Akt was a temporary classification name for a mouse that developed spontaneous thymic lymphomas. The 't' stands for '; the letter was added when a transforming retrovirus was isolated from the Ak strain, which was termed 'Akt-8'. Free rapidshare downloads.

When the oncogene encoded in this virus was discovered, it was termed v-Akt. Thus, the later identified human analogues were named accordingly. [ ] Regulation [ ] Akt1 is involved in the and other signaling pathways. [ ] Binding phospholipids [ ] Akt possesses a known as a PH domain, or, named after, the protein in which it was first discovered.

This domain binds to with high affinity. In the case of the PH domain of Akt, it binds either PIP 3 (, PtdIns(3,4,5) P 3) or PIP 2 (, PtdIns(3,4) P 2). This is useful for control of cellular signaling because the di-phosphorylated phosphoinositide is only phosphorylated by the family of enzymes, PI 3-kinases ( or PI3-K), and only upon receipt of chemical messengers which tell the cell to begin the growth process.

For example, PI 3-kinases may be activated by a or such as the. Once activated, PI 3-kinase phosphorylates PIP 2 to form PIP 3.

Phosphorylation [ ] Once correctly positioned at the membrane via binding of, Akt can then be phosphorylated by its activating kinases, phosphoinositide dependent kinase 1 ( at threonine 308) and the mammalian target of rapamycin complex 2 ( at serine 473), first by mTORC2. MTORC2 therefore functionally acts as the long-sought PDK2 molecule, although other molecules, including (ILK) and mitogen-activated protein kinase-activated protein kinase-2 () can also serve as PDK2. Phosphorylation by mTORC2 stimulates the subsequent phosphorylation of Akt by PDPK1. Activated Akt can then go on to activate or deactivate its myriad substrates (e.g. ) via its kinase activity. Besides being a downstream effector of PI 3-kinases, Akt can also be activated in a PI 3-kinase-independent manner. Or, a non-receptor tyrosine kinase, phosphorylates Akt at its tyrosine 176 residue, leading to its activation in PI 3-kinase-independent manner.