Cell Biology

                             phosphatidylinositide 3-kinases

Family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, and at last in cancer.

PI3Ks are intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol. The pathway, with oncogene and tumor suppressor is involved in insensitivity of cancer tumors to insulin and IGF1, in calorie restriction.

G protein–coupled receptors (GPCRs)

Other names:  seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein–linked receptors (GPLR).

They are from large protein family of receptors that sense molecule outside the cell and activate inside signal transduction pathways and cellular responses. They are called seven-transmembrane receptors because they pass through the cell membrane seven times.

G protein–coupled receptors are found only in eukaryotes, including yeast and animals. 

The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters. It varies in size from small molecules to peptides to large proteins. G protein–coupled receptors are involved in many diseases, and are also the target of approximately 40% of all modern medicinal drugs.

There are two principal pathways involving the GPCRs:

·          cAMP signal pathway and

·         Phosphatidylinositol signal pathway.  

When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate G protein by exchanging its bound GDP for a GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type.

 Ryanodine receptors (RyRs)

They are class of intracellular calcium channel in muscles and neurons. It is the major cellular mediator of calcium induced calcium release (CICR) in animal cells.

There are multiple isoforms of ryanodine receptors:

• RyR1 is expressed in skeletal muscles.
• RyR2 is expressed in heart muscle.
• RyR3 is expressed more widely, but especially in the brain.

Ryanodine receptors mediate the release of calcium ions from the ER, an essential step in muscle contraction. In skeletal muscle it is thought that activation occurs via a physical coupling to the dihydrphyridin receptors, whereas, in cardiac muscle, the primary mechanism is calcium-induce calcium release from the sarcoplasmic reticulum.