Akt family of serine/threonine-directed kinases regulates
a diverse array of biological processes, including cellular survival,
proliferation, glucose homeostasis, and vascular tone and are important molecules in mammalian
cellular signaling. The three widely expressed isoforms of
PKB (PKB
, PKBß and PKB
; also known as Akt1, Akt2 and
Akt3, respectively) are each composed of an N-terminal PtdIns(3,4,5)P3-
and PtdIns(3,4)P2-binding PH domain and a
C-terminal kinase catalytic domain. Stimulation by numerous growth factors,
cytokines, hormones and neurotransmitters can activate PKB/Akt in a
phosphoinositide 3-kinase-dependent manner. Through receptor tyrosine kinases,
these stimuli cause phosphoinositide 3-kinase activation, and generation of the
membrane phospholipid PtdIns(3,4,5)P3. PtdIns(3,4,5)P3 then
recruits PKB/Akt to the membrane, where it becomes phosphorylated (for PKBa/Akt1) by upstream kinases,
phosphoinositide-dependent kinase 1. Following the activation of PI
3-kinase, PKB isoforms are recruited from the cytosol to the plasma
membrane through their interaction with PtdIns(3,4,5)P3
and/or PtdIns(3,4)P2 where they are thought to
undergo a conformational change and become activated by phosphorylation of
two residues. PKB can promote cell survival by inhibiting proteins that mediate
apoptosis. Phosphorylation of BAD by PKB (and other AGC kinases)
enables it to interact with 14-3-3 proteins, which prevents it from
binding to Bcl-XL and thereby suppresses apoptosis. It
directly phosphorylate and inhibit the caspase proteasesm, key executioners of
apoptosis. PKBbeta, an essential gene for the maintenance of
normal glucose homeostasis and is likely to represent a critical intermediate
in the insulin signal transduction pathway. PKB activation
might inhibit apoptosis by promoting the increased expression of
survival molecules or the degradation of pro-apoptotic molecules. PKB also
phosphorylates and activates endothelial nitric oxide synthase,
thereby promoting angiogenesis (formation of new blood vessels).
Inhibition of GSK3 following its phosphorylation by PKB has also
been suggested to play a role in inhibiting apoptosis in neuronal
cells. Thus it plays a key role in cancer progression by stimulating cell proliferation
and inhibiting apoptosis, which suggests it, likely to be a hot drug target for
the treatment of cancer, diabetes and stroke.
IMGENEX India
Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern
India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA.
Find out more information about Akt Family.
stephen jones
IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India.