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Concept
Protein kinase B
Summary
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.
There are three different genes that encode isoforms of Protein kinase B. These three genes are referred to as AKT1, AKT2, and AKT3 and encode the RAC alpha, beta, and gamma serine/threonine protein kinases respectively. The terms PKB and Akt may refer to the products of all three genes collectively, but sometimes are used to refer to PKB alpha and Akt1 alone.
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. A mouse model with complete deletion of the Akt1 gene 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. Akt1 was originally identified as the oncogene in the transforming retrovirus, AKT8.
Akt2 is an important signaling molecule in the insulin signaling pathway. 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 diabetic phenotype (insulin resistance), again consistent with the idea that Akt2 is more specific for the insulin receptor signaling pathway.
The role of Akt3 is less clear, though it appears to be predominantly expressed in the brain. It has been reported that mice lacking Akt3 have small brains.
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