Protein kinase B

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PKB (also known as Akt) is a Serine/Threonine [[Protein kinase|protein kinase]] involved in various cellular processes such as [[Glucose|glucose]] [[Metabolism|metabolism]], cell proliferation and survival.  
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PKB (also known as Akt) is a 57-kDa Serine/Threonine [[Protein kinase|protein kinase]] which comes from the AGC subfamily of the protein kinase super family<ref>Journal of Cell Sciece. Protein kinase B/Akt at a glance. 2005 [cited: 26/10/18] Available from:http://jcs.biologists.org/content/118/24/5675.article-info</ref>. It is a key component for various cellular processes such as [[Glucose|glucose]] [[Metabolism|metabolism]], cell proliferation, transcription and survival.  
  
 
== Insulin and PKB  ==
 
== Insulin and PKB  ==
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=== Protein Synthesis  ===
 
=== Protein Synthesis  ===
  
PKB phosphorylates TSC2 ([[Tuberous sclerosis complex 2|Tuberous sclerosis complex 2]])&nbsp;which therefore becomes inactivated. This is a [[GTPase Activating Protein|GTPase Activating Protein]] which phosphorylates and inactivates [[Rheb|Rheb]] – a small [[G-proteins|G protein]]. This means that phosphorylation of TSC2 by PKB allows activation of Rheb and the completion of the mTor pathway leading to increased [[Transcription|transcription]] by activation of p70 ribosomal protein S6 kinase (S6K1). PKB therefore increases [[Protein synthesis|protein synthesis]].  
+
PKB phosphorylates TSC2 ([[Tuberous sclerosis complex 2|Tuberous sclerosis complex 2]]) which therefore becomes inactivated. This is a [[GTPase Activating Protein|GTPase Activating Protein]] which phosphorylates and inactivates [[Rheb|Rheb]] – a small [[G-proteins|G protein]]. This means that [[Phosphorylation|phosphorylation]] of TSC2 by PKB allows activation of Rheb and the completion of the mTor pathway leading to increased [[Transcription|transcription]] by activation of p70 ribosomal protein S6 kinase (S6K1). PKB therefore increases [[Protein synthesis|protein synthesis]].  
  
 
=== Glycogen Synthesis  ===
 
=== Glycogen Synthesis  ===
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=== Effect on lipolysis  ===
 
=== Effect on lipolysis  ===
  
PKB decreases [[Lipolysis|lipolysis]] by activation of [[Phosphodiesterase|phosphodiesterase]] 3B (PDE3B). This [[Enzyme|enzyme]] is responsible for the breakdown of [[CAMP|cAMP]] to [[AMP|5’AMP]] resulting in less activation of [[Protein kinase A|protein kinase A]]&nbsp;(PKA). PKA usually phosphorylates (and activates) [[Hormone Sensitive Lipase|Hormone Sensitive Lipase]]&nbsp;(HSL) which converts [[Triacylglycerides|triacylglycerides]] into free [[Fatty acid|fatty acids]] and [[Glycerol|glycerol]]. Since there is less activation of HSL with less PKA, lipolysis is reduced. This effect is further established by reduced [[Phosphorylation|phosphorylation]] of perilipin by PKA. This is a protein bound to the surface of fat droplets in adipocytes which prevent lipolysis by blocking HSL access.<br>
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PKB decreases [[Lipolysis|lipolysis]] by activation of [[Phosphodiesterase|phosphodiesterase]] 3B (PDE3B). This [[Enzyme|enzyme]] is responsible for the breakdown of [[CAMP|cAMP]] to [[AMP|5’AMP]] resulting in less activation of [[Protein kinase A|protein kinase A]] (PKA). PKA usually phosphorylates (and activates) [[Hormone Sensitive Lipase|Hormone Sensitive Lipase]] (HSL) which converts [[Triacylglycerides|triacylglycerides]] into free [[Fatty acid|fatty acids]] and [[Glycerol|glycerol]]. Since there is less activation of HSL with less PKA, [[Lipolysis|lipolysis]] is reduced. This effect is further established by reduced [[Phosphorylation|phosphorylation]] of perilipin by PKA. This is a protein bound to the surface of fat droplets in adipocytes which prevent lipolysis by blocking HSL access.  
  
 
== Implications in disease  ==
 
== Implications in disease  ==
  
There is concern over the expression or mutation of the PI3K-Akt pathway due to its involvement in other important cellular processes such as cell proliferation, survival and growth.&nbsp;In many tumour cells, there is hyperactivation of this pathway, suggesting inhibitors of this pathway could help prevent growth of tumour cells and therefore contribute towards the treatment of human cancer<ref>Luo Ji, Manning Brendan D, Cantley Lewis C (2003) Targeting the PI3K-Akt pathway in human cancer: Rationale and promise; Cancer Cell; 4 (4) 257-262</ref>.<br>As well as its role in [[Diabetes|diabetes]] and cancer, dysfunctional PKB regulation is now implied in [[Schizophrenia|Schizophrenia]] as well as some neurodegenerative disorders such as [[Huntington’s disease|Huntington’s disease]]&nbsp;and [[Alzheimer's disease|Alzheimer’s disease]]&nbsp;due to its role in the growth and protection of [[Neuron|neuronal cells]]<ref>Franke T.F. (2008) PI3K/Akt: getting it right matters; Oncogene 27: 6473-6488</ref>. <br>
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There is concern over the expression or mutation of the PI3K-Akt pathway due to its involvement in other important cellular processes such as cell proliferation, survival and growth. In many tumour cells, there is hyperactivation of this pathway, suggesting inhibitors of this pathway could help prevent growth of tumour cells and therefore contribute towards the treatment of human cancer<ref>Luo Ji, Manning Brendan D, Cantley Lewis C (2003) Targeting the PI3K-Akt pathway in human cancer: Rationale and promise; Cancer Cell; 4 (4) 257-262</ref>. As well as its role in [[Diabetes|diabetes]] and cancer, dysfunctional PKB regulation is now implied in [[Schizophrenia|Schizophrenia]] as well as some neurodegenerative disorders such as [[Huntington’s disease|Huntington’s disease]] and [[Alzheimer's disease|Alzheimer’s disease]] due to its role in the growth and protection of [[Neuron|neuronal cells]]<ref>Franke T.F. (2008) PI3K/Akt: getting it right matters; Oncogene 27: 6473-6488</ref>.  
  
=== References  ===
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== References  ==
  
 
<references />
 
<references />

Latest revision as of 11:05, 30 October 2018

PKB (also known as Akt) is a 57-kDa Serine/Threonine protein kinase which comes from the AGC subfamily of the protein kinase super family[1]. It is a key component for various cellular processes such as glucose metabolism, cell proliferation, transcription and survival.

Contents

Insulin and PKB

PKB is phosphorylated at two sites and therefore activated by 3-phosphoinositide dependent protein kinase (PDK). PDK is a kinase associated with the plasma membrane (PDK binds PIP3 via its PH domain) and activated by Protein Kinase C (PKC) as a result of the PI3K pathway. Although the exact mechanism is unknown, this pathway is associated with the translocation of GLUT4 transporters to the plasma membrane, enabling uptake of glucose into the cell.

Protein Synthesis

PKB phosphorylates TSC2 (Tuberous sclerosis complex 2) which therefore becomes inactivated. This is a GTPase Activating Protein which phosphorylates and inactivates Rheb – a small G protein. This means that phosphorylation of TSC2 by PKB allows activation of Rheb and the completion of the mTor pathway leading to increased transcription by activation of p70 ribosomal protein S6 kinase (S6K1). PKB therefore increases protein synthesis.

Glycogen Synthesis

PKB also phosphorylates glycogen synthase kinase 3 (GSK3) which then becomes inactivated. This means GSK3 is no longer available to inactivate glycogen synthase which incorporates UDP-glucose into a chain of glycogen for storage. PKB therefore increases glycogen synthesis.

Effect on lipolysis

PKB decreases lipolysis by activation of phosphodiesterase 3B (PDE3B). This enzyme is responsible for the breakdown of cAMP to 5’AMP resulting in less activation of protein kinase A (PKA). PKA usually phosphorylates (and activates) Hormone Sensitive Lipase (HSL) which converts triacylglycerides into free fatty acids and glycerol. Since there is less activation of HSL with less PKA, lipolysis is reduced. This effect is further established by reduced phosphorylation of perilipin by PKA. This is a protein bound to the surface of fat droplets in adipocytes which prevent lipolysis by blocking HSL access.

Implications in disease

There is concern over the expression or mutation of the PI3K-Akt pathway due to its involvement in other important cellular processes such as cell proliferation, survival and growth. In many tumour cells, there is hyperactivation of this pathway, suggesting inhibitors of this pathway could help prevent growth of tumour cells and therefore contribute towards the treatment of human cancer[2]. As well as its role in diabetes and cancer, dysfunctional PKB regulation is now implied in Schizophrenia as well as some neurodegenerative disorders such as Huntington’s disease and Alzheimer’s disease due to its role in the growth and protection of neuronal cells[3].

References

  1. Journal of Cell Sciece. Protein kinase B/Akt at a glance. 2005 [cited: 26/10/18] Available from:http://jcs.biologists.org/content/118/24/5675.article-info
  2. Luo Ji, Manning Brendan D, Cantley Lewis C (2003) Targeting the PI3K-Akt pathway in human cancer: Rationale and promise; Cancer Cell; 4 (4) 257-262
  3. Franke T.F. (2008) PI3K/Akt: getting it right matters; Oncogene 27: 6473-6488
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