User:Tarangupadhyaya/sandbox

Background.

Protein kinase A or also known as cAMP-dependent protein kinase was discovered by chemists H. Fischer and Edwin G. Krebs in 1968. They won the Nobel Prize in Physiology or Medicine in 1992 for their work on phosphorylation and desphosphorylation and how it is relates to protein kinase A activity.

PKA is one of the most widely researched protein Kinase because of its uniqueness; out 540 different protein kinase genes that make up for human kinome, only one other protein kinase; CK2 exists in a tetramer complex.

The diversity of mammalian PKA subunits were realized after Dr. Stan Knight and others identified possible four subunit C genes and presence of four R subunit genes. In 1991; Susan Taylor and et. Al crystallized PKA Cα subunit which revealed bi-lobe structure of kinase core for the very first time.

In Skeletal Muscle

Protein Kinase A is directed to specific sub cellular locations after tethering to Protein kinase A anchoring proteins (AKAPs). Sacroplasmic Reticulum Ca2+ release channel or Ryanodine receptor (Ryr) co-localizes with the muscle AKAP. RyR phosohorylation and efflux of Ca 2+ is increased by localisation of PKA at RyR by mAKP.

Modulation of ethanol consumption

Protein Kinase A signal transduction pathway helps in modulation of ethanol consumption and its sedative effects. A mouse study reports that mice with genetically reduced cAMP-PKA signalling results into less consumption of ethanol and are more sensitive to its sedative effects.

In formation of memories

PKA has always been considered important in formation of a memory. Reductions in expression activity of DCO (PKA catalytic subunit encoding gene) can cause severe learning disabilities, middle term memory and short term memory. Long term memory is dependent on the CREB transcription factor, regulated by PKA. A study done on drosophila reported that an increase in PKA activity can effect short term memory. However, a decrease in PKA activity by 24% inhibited learning abilities and a decrease by 16% affected both learning ability and memory retention. Formation of a normal memory is highly sensitive to PKA levels.