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Second Messengers. Glucose Mobilization- cAMP. A second Major signalling Pathway. Glucagon + Epinephrine (Hormone) acts on liver cells ----------- promotes release of glucose to blood stream. Insulin acts on liver and muscle cells to initiate an opposite series of reaction.

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a second major signalling pathway
A second Major signalling Pathway
  • Glucagon + Epinephrine (Hormone) acts on liver cells ----------- promotes release of glucose to blood stream.
  • Insulin acts on liver and muscle cells to initiate an opposite series of reaction.

(i.e) glucose is removed from blood stream and polymerized as glycogen.

  •  Insulin is powerful stimulant of lipid synthesis, protein synthesis as well as for cell growth and cell proliferation.
  • Insulin elicits this response by means of signalling pathway.
mechanism of insulin action signalling rtk
Mechanism of Insulin Action: Signalling RTK

Insulin Receptor:

  • Cell responds to insulin by receptor at cell surface.
  • Insulin receptor binds to ligand by an enzyme Protein Tyrosine Kinasealso referred as Receptor Tyrosine kinase-RTK.

Insulin Receptor:

  • Is a tetrameric protein composed of two alpha and two beta poypeptide chains linked by disulphide bonds.
  • Alpha Chain - reside on membrane surface on insulin binding site
  • Beta chain - span lipid bilayer and transmit signal across membrane to inner surface.
  • In absence of bound insulin ,tyrosine kinase function will be inactive.
  • To activate Insulin Receptor Substrate(IRS) transfer phosphate group by autophosphorylation.
  • ‘ras’ is a viral oncogene carried by tumor viruses that transform normal cell to malignant cells.
  • Further research showed: like other oncogene ‘ras’ also present in normal genome of animal including human (mutant variety).
  • Ras is a small ‘G’ protein held at inner surface of plasma membrane by a lipid group.
  • It cycles between inactive GDP bound to GTP bound active form.
  • Ras activity is controlled by GTP back to bound GDP form , so ras remain in ‘on’ position allowing abnormal or disease proliferation.
map kinase pathway map mitogen activated protein
MAP Kinase Pathway: [MAP-Mitogen activated protein]

also called as rassignalingpathway

A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.

  • Binding of growth factor to RTK(Insulin Receptor)
  • Phosphotyrosine generates at cytoplasmic domain act as binding site for SH2 protein called Grb2.
  • (Grb2 is not a protein but act as adaptor molecule links other protein into complex)
  • Grb2 molecule binds to phosphorylate RTK at inner surface of membrane, where sos protein binds to it on another domain.
  • (sos protein Is guanine nucleotide exchange factor for ras (i.e) ras-GEF exchange of GDP to GTP).
  • In Unstimulated cells Ras bound to GDP (inactive form)
  • When these ligand bind to RTK, Grb2 - sos on inner membrane lose GDP and replaced by GTP thus activate ras.(ras- GTP).
  • Sole function of ras-GTP is to add another protein called Raf to plasma membrane which initiates chain of phosphorylation reaction called MAP Kinase cascade.

MAP Kinase cascade-similar to cAMP- Both cAMP & MAP Kinase is extracellular signals influence gene expression