The cell, has many pathways to avoid a process called Apoptosis. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis, in general, confers advantages during an organism’s life cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytic cells are able to engulf and quickly remove before the contents of the cell can spill out onto surrounding cells and cause damage. But many cells, can avoid this natural pathway and keep on proliferating, growing… CAN YOU REMEMBER SOMETHING LIKE THIS?
YEAP, CANCER…. Cancer cells have the skill to runaway from apoptosis. One of the main «roads» to follow it is a pathway called: The Akt/PKB signaling pathway. Akt/PKB is a pathway in cell signaling.

 

Proteins involved include AKT (also known as “protein kinase B”, PKB) and phosphoinositide 3-kinase (PI3K).

PI3 Kinase is a lipid kinase that is activated (via an SH2-domain adaptor) by signals (e.g., members of the insulin-like growth factor (IGF) family of signal proteins) transmitted by many transmembrane receptors with protein kinase cytosolic domains. This activation leads to production from membrane inositol of the inositol phospholipids PtdIns(3,4,5)P3 and PtdIns(3,4)P2

As you can see on the picture, there are several molecules that naturaly follow some activating/inhibiting pathawys. This complex phosphorylates many highly significant substrates. Akt indirectly activates (not phosphorylates) mTOR, which lies at the heart of growth regulatory pathways.

mTOR promotes cell growth by:

– activating S6kinase (an activator of translation)

– activating PKC (so turning on many synthetic and secretory pathways)

– inhibiting p21 (so releasing cells from G1 arrest)

– inhibiting GSK3β (with similar effect, since GSK3β targets cyclin D for proteolysis)

Akt also phosphorylates Bad (a pro-apoptotic protein,which in its non-phosphorylated state, promotes apoptosis) which sequesters it and keeps it out of action, promoting cell survival.