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Second Messengers

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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Second Messengers

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  1. Second Messengers

  2. Glucose Mobilization- cAMP

  3. 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.

  4. 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.

  5. Ras: • ‘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.

  6. 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.

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

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