Insulin Signaling Pathway [PI-3 kinase pathway]

The insulin signaling pathway follows the principles of the PI-3 kinase pathway.

The structure of the Insulin receptor (INS-R):

The insulin receptor (INS-R) is a receptor tyrosine kinase. The receptor consists of two α subunits on the outer face of the plasma membrane and two transmembrane β subunits. The two α-subunits are connected by disulfide bonds. There is a single disulfide bond the α- and β- subunits also.

Insulin Signaling Pathway- The Mechanism of Action:

1. Binding of insulin to the α-subunits triggers a confirmational change that allows the auto phosphorylation of tyrosine residues in the carboxyl-terminal domain of the β-subunits.
2. The phosphorylated insulin receptor next phosphorylates Insulin Receptor Substrates (IRS) on tyrosine residues. Phosphorylated IRS binds to the SH2 domains of a variety of proteins that are directly involved in mediating different effects of insulin.
3. The phosphorylated IRS molecule acts as docking site for enzyme PI-3 kinase.
4. The PI-3 kinase then phosphorylates PI- 3,4 biphosphate (PIP2) leading to the formation of PI 3,4, 5-triphosphate (PIP3). Binding of PIP3 with PKB leads to the activation of PKB.
5. The activated PKB phosphorylates glycogen synthase kinase 3 (GSK3) and inactivate it. Inactivation of GSK3 makes the glycogen synthase active which triggers the synthesis glycogen from glucose.
6. In muscle and fat tissue m, PKB also triggers the movement of glucose transporters (GLUT4) from internal vesicles to the plasma membrane, stimulating glucose uptake from the blood.

The word diagram of the Insulin Signaling pathway:

The Insulin receptor triggers the other signaling pathways:

Other signal transduction proteins interact with the IRS including GRB2, an adaptor protein that contains SH3 domains, which in turn associate with the SOS and elicit activation of the monomeric G-protein, RAS. RAS activates the MAP kinase pathway leading to the mitogenic responses.

Other related notes:

1. RAS-MAP kinase pathway: https://thebiologyislove.com/ras-map-kinase-pathway/
2. PI-3 kinase pathway: https://thebiologyislove.com/pi-3-kinase-pathway/

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