Hi All
To continue with signal transduction...
Another pathway includes PIP2 which is phosphatidyl inositol biphosphate. It exist in inner plasma membrane.
Phospholipase C acts on PIP2 and convert it into DAG(diacyl glycerol) and IP3(inositol 1,4,5 triphosphate).
DAG remain attach to plasma membrane and IP3 is diffused in cytosol.
DAG activate PKC protein kinase C.
DAG controls cell differentiation, cell growth and cell death.
It serve as transcriptional activator.
DAG can be further cleaved to give arachidonic acid.
IP3 acts as a signal which binds to IP3 gated calcium release channel on endoplasmic reticulum.It releases calcium in cytoplasm from endoplasmic reticulum.
Calcium is secondary messanger and can activate several protein kinase.
One target of calcium is calmodulin.
Calmodulin has two arms and each arm has two calcium binding sites.
When calcium level are lower than calcium is released from calmodulin but when calcium is higher (as in reponse to IP3) calcium binds to calmodulin and its confirmation gets changed and gets activated.
Calmodulin is also known as CaM kinase or calcium dependent protein kinase.
CaM is present in nervous system of most animals and is involved in learning and memory.
CaM also regulate gene expression.
AKT pathway.
It involves PI3 kinase(phosphatidyl inositol-3 kinase).It converts PIP2 into PIP3.
AKT is serine threonine kinase and is activated by PIP3.
IGF insulin growth factor signal AKT pathway.
IGF bind to receptor tyrosine kinase and activate PIP3 kinase.
PIP3 is kinase and it recruit AKT and PDK-1.So AKT gets activated.
Target of AKT is FOXO protein which is a transcription factor.
When FOXO is unphosphorylated, it enters nucleus and cause transcription of those genes which are required in cell deat etc.
But when phosphorylated by AKT, FOXO becomes inactive and cannot translocate to nucleus hence no response.
Another target of AKT is GSK3 beta kinase.
GSK 3 beta is active when unphosphorylated. It phosphorylate target and regulates cell proliferation and cell survival.
When signal comes or AKT phophorylate GSK3 beta it becomes inactive.
MAP or ERK pathway
It is also known as mitogen activator protein because it involves Ras protein.
ERK extra cellular signal regulated kinase.
ERK can be activated by GPCR or tyrosine kinase receptor.
In case of receptor tyrosine kinase, when signal activates receptor tyrosine kinase, it dimerizes and autophosphorylation.
Then ovel sites are exposed and they recruit Ras Guanine nucleotide exchange factor or Ras GEF.
Ras GEF has SH2 domain which is called Grb2 domain.
Cytoplasm has Raf protein. And Raf is activated by Ras GEF.
Target of Raf are another protein kinase called MEK or MAP/ERK kinase.
MEK phosphorylate MAP.
To continue with signal transduction...
Another pathway includes PIP2 which is phosphatidyl inositol biphosphate. It exist in inner plasma membrane.
Phospholipase C acts on PIP2 and convert it into DAG(diacyl glycerol) and IP3(inositol 1,4,5 triphosphate).
DAG remain attach to plasma membrane and IP3 is diffused in cytosol.
DAG activate PKC protein kinase C.
DAG controls cell differentiation, cell growth and cell death.
It serve as transcriptional activator.
DAG can be further cleaved to give arachidonic acid.
IP3 acts as a signal which binds to IP3 gated calcium release channel on endoplasmic reticulum.It releases calcium in cytoplasm from endoplasmic reticulum.
Calcium is secondary messanger and can activate several protein kinase.
One target of calcium is calmodulin.
Calmodulin has two arms and each arm has two calcium binding sites.
When calcium level are lower than calcium is released from calmodulin but when calcium is higher (as in reponse to IP3) calcium binds to calmodulin and its confirmation gets changed and gets activated.
Calmodulin is also known as CaM kinase or calcium dependent protein kinase.
CaM is present in nervous system of most animals and is involved in learning and memory.
CaM also regulate gene expression.
AKT pathway.
It involves PI3 kinase(phosphatidyl inositol-3 kinase).It converts PIP2 into PIP3.
AKT is serine threonine kinase and is activated by PIP3.
IGF insulin growth factor signal AKT pathway.
IGF bind to receptor tyrosine kinase and activate PIP3 kinase.
PIP3 is kinase and it recruit AKT and PDK-1.So AKT gets activated.
Target of AKT is FOXO protein which is a transcription factor.
When FOXO is unphosphorylated, it enters nucleus and cause transcription of those genes which are required in cell deat etc.
But when phosphorylated by AKT, FOXO becomes inactive and cannot translocate to nucleus hence no response.
Another target of AKT is GSK3 beta kinase.
GSK 3 beta is active when unphosphorylated. It phosphorylate target and regulates cell proliferation and cell survival.
When signal comes or AKT phophorylate GSK3 beta it becomes inactive.
MAP or ERK pathway
It is also known as mitogen activator protein because it involves Ras protein.
ERK extra cellular signal regulated kinase.
ERK can be activated by GPCR or tyrosine kinase receptor.
In case of receptor tyrosine kinase, when signal activates receptor tyrosine kinase, it dimerizes and autophosphorylation.
Then ovel sites are exposed and they recruit Ras Guanine nucleotide exchange factor or Ras GEF.
Ras GEF has SH2 domain which is called Grb2 domain.
Cytoplasm has Raf protein. And Raf is activated by Ras GEF.
Target of Raf are another protein kinase called MEK or MAP/ERK kinase.
MEK phosphorylate MAP.
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