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Protein Kinase A&nbsp;(PKA) is a [[Proteins|protein]] that is dependent on [[CAMP|cyclic AMP]] ([[CAMP|cAMP]]) and without it, is deactivated. PKA is involved in [[Signal-transduction pathway|signal-transduction pathways]] and [[Phosphorylation|phosphorylates]] [[Proteins|proteins]] by adding a [[Phosphate group|phosphate group]]. The [[Molecule|molecule]] consists of two subunits, a regulatory subunit and a calalytic subunit <ref>Berg, J. Tymoczko, J. and Stryer, L. (2007) Biochemistry, 6th edition, New York: WH Freeman</ref>. These subunits are inactive when [[CAMP|cAMP]]&nbsp;is not bound. When [[CAMP|cAMP]]&nbsp;binds to a regulatory subunit a conformational change occurs. This change means that the catalytic subunit becomes active and is no longer inhibited. This means that the protein can now [[Phosphorylation|phosphorylate]] other [[Proteins|proteins]] by removing a phosphate from [[ATP]], and adding it to a [[Serine|serine]] residue on the target [[Protein|protein]] which in turn leads to a cellular response <ref>http://www.vivo.colostate.edu/hbooks/molecules/pka.html</ref>.  
Protein Kinase A&nbsp;(PKA) is a [[Proteins|protein]] that is dependent on [[CAMP|cyclic AMP]] ([[CAMP|cAMP]]) and without it, is deactivated. PKA is involved in [[Signal-transduction pathway|signal-transduction pathways]] and [[Phosphorylation|phosphorylates]] [[Proteins|proteins]] by adding a [[Phosphate group|phosphate group]]. The [[Molecule|molecule]] consists of two subunits, a regulatory subunit and a calalytic subunit <ref>Berg, J. Tymoczko, J. and Stryer, L. (2007) Biochemistry, 6th edition, New York: WH Freeman</ref>. These subunits are inactive when [[CAMP|cAMP]]&nbsp;is not bound. When [[CAMP|cAMP]]&nbsp;binds to a regulatory subunit a conformational change occurs. This change means that the catalytic subunit becomes active and is no longer inhibited. This means that the protein can now [[Phosphorylation|phosphorylate]] other [[Proteins|proteins]] by removing a phosphate from [[ATP]], and adding it to a [[Serine|serine]] residue on the target [[Protein|protein]] which in turn leads to a cellular response <ref>http://www.vivo.colostate.edu/hbooks/molecules/pka.html</ref>.  


Protein Kinase A (PKA) is one of the member of family of [[Enyzmes|enyzmes]] which is functionally dependent on the levels of cyclic-adenomonophopshate ([[CAMP|cAMP]]). It is also commonly known as the cAMP dependent A kinase, therefore it works through the cAMP signalling pathway. Essentially, PKA is responsible for all the cellular responses induced by cAMP second messenger system.<br>  
Protein Kinase A (PKA) is one of the member of family of [[Enzyme|enyzmes]] which is functionally dependent on the levels of cyclic-adenomonophopshate ([[CAMP|cAMP]]). It is also commonly known as the cAMP dependent A kinase, therefore it works through the cAMP signalling pathway. Essentially, PKA is responsible for all the cellular responses induced by cAMP second messenger system.<br>


=== Structure:  ===
=== Structure:  ===
Line 13: Line 13:
=== Regulation of activity:  ===
=== Regulation of activity:  ===


When cAMP levels are low, the catalytic subunits are bound to the regulatoy subunit dimer and are inactive. Each regulatory subunit contains a sequence which matches the [[Phosphorylation|phosphorylation]] [[Consensus_sequence|consensus sequence]] - pseudo-substrate motif ([[Arginine|Arg]]-[[Arginine|Arg]]-[[Glycine|Gly]]-[[Alanine|Ala]]-[[Isoleucine|Ile]]). This sequence therefore enters the [[Enzyme_active_site|active site]] of the catalytic subunit, preventing any substrate from entering the [[Enzyme_active_site|active site]], inhibiting the enzyme&nbsp;<ref>Berg, J. Tymoczko, J. and Stryer, L. (2012) Biochemistry, 7th edition, New York: WH Freeman</ref>.&nbsp;As the concentration of cAMP increases, 2 cAMP molecules<ref>Berg, J. Tymoczko, J. and Stryer, L. (2012) Biochemistry, 7th edition, New York: WH Freeman</ref>&nbsp;bind to each of the regulatory subunits, causing a conformational change of the catalytic subunits from an inactive toa n active form <ref>R. Bowen, November 28 2003, Hypertexts for Biomedical Sciences, a resource of Colorado State University</ref><ref>http://www.vivo.colostate.edu/hbooks/molecules/pka.html</ref>.
When cAMP levels are low, the catalytic subunits are bound to the regulatoy subunit dimer and are inactive. Each regulatory subunit contains a sequence which matches the [[Phosphorylation|phosphorylation]] [[Consensus sequence|consensus sequence]] - pseudo-substrate motif ([[Arginine|Arg]]-[[Arginine|Arg]]-[[Glycine|Gly]]-[[Alanine|Ala]]-[[Isoleucine|Ile]]). This sequence therefore enters the [[Enzyme active site|active site]] of the catalytic subunit, preventing any substrate from entering the [[Enzyme active site|active site]], inhibiting the enzyme&nbsp;<ref>Berg, J. Tymoczko, J. and Stryer, L. (2012) Biochemistry, 7th edition, New York: WH Freeman</ref>.&nbsp;As the concentration of cAMP increases, 2 cAMP molecules<ref>Berg, J. Tymoczko, J. and Stryer, L. (2012) Biochemistry, 7th edition, New York: WH Freeman</ref>&nbsp;bind to each of the regulatory subunits, causing a conformational change of the catalytic subunits from an inactive toa n active form <ref>R. Bowen, November 28 2003, Hypertexts for Biomedical Sciences, a resource of Colorado State University</ref><ref>http://www.vivo.colostate.edu/hbooks/molecules/pka.html</ref>.  


=== References  ===
=== References  ===


<references /><br>
<references /><br>

Revision as of 12:56, 28 November 2012

Protein Kinase A (PKA) is a protein that is dependent on cyclic AMP (cAMP) and without it, is deactivated. PKA is involved in signal-transduction pathways and phosphorylates proteins by adding a phosphate group. The molecule consists of two subunits, a regulatory subunit and a calalytic subunit [1]. These subunits are inactive when cAMP is not bound. When cAMP binds to a regulatory subunit a conformational change occurs. This change means that the catalytic subunit becomes active and is no longer inhibited. This means that the protein can now phosphorylate other proteins by removing a phosphate from ATP, and adding it to a serine residue on the target protein which in turn leads to a cellular response [2].

Protein Kinase A (PKA) is one of the member of family of enyzmes which is functionally dependent on the levels of cyclic-adenomonophopshate (cAMP). It is also commonly known as the cAMP dependent A kinase, therefore it works through the cAMP signalling pathway. Essentially, PKA is responsible for all the cellular responses induced by cAMP second messenger system.

Structure:

PKA is a heterotetramer consists of 4 subunits, of which composed of 2 regulatory and 2 catalytic subunits.

  • Regulatory subunit: Two of these subunits are joined together covalently via disulfide bonds. Each subunit has 2 cAMP binding sites, a domain that interacts with the catalytic subunit and a "auto-inhibitory" domain that act as a pseudo-substrate motif RRGA1 for the catalytic subunit. Two major forms of regulatory subunits exist, RI and RII, each form has two subtypes alpha and beta, while each isotype is encoded by different genes. 
  • Catalytic subunit: This subunit contains the ATP binding domain and the enzyme's active site. Each subunit is bound to the either side of the regulatory subunit. There are three isotypes which have been identified for the catalytic subunit(alpha beta and gamma). 

Regulation of activity:

When cAMP levels are low, the catalytic subunits are bound to the regulatoy subunit dimer and are inactive. Each regulatory subunit contains a sequence which matches the phosphorylation consensus sequence - pseudo-substrate motif (Arg-Arg-Gly-Ala-Ile). This sequence therefore enters the active site of the catalytic subunit, preventing any substrate from entering the active site, inhibiting the enzyme [3]. As the concentration of cAMP increases, 2 cAMP molecules[4] bind to each of the regulatory subunits, causing a conformational change of the catalytic subunits from an inactive toa n active form [5][6].

References

  1. ↑ Berg, J. Tymoczko, J. and Stryer, L. (2007) Biochemistry, 6th edition, New York: WH Freeman
  2. ↑ http://www.vivo.colostate.edu/hbooks/molecules/pka.html
  3. ↑ Berg, J. Tymoczko, J. and Stryer, L. (2012) Biochemistry, 7th edition, New York: WH Freeman
  4. ↑ Berg, J. Tymoczko, J. and Stryer, L. (2012) Biochemistry, 7th edition, New York: WH Freeman
  5. ↑ R. Bowen, November 28 2003, Hypertexts for Biomedical Sciences, a resource of Colorado State University
  6. ↑ http://www.vivo.colostate.edu/hbooks/molecules/pka.html


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