Place all eight of these steps of the insulin signaling pathway in the correct order. The abbreviation PIP 2 is used for phosphatidylinositol 4,5‑bisphosphate, and PIP 3 is used for phosphatidylinositol 3,4,5‑trisphosphate.

1. Activation of Akt
2. Binding of insulin to the alpha subunit of the insulin receptor
3. Phosphorylation of IRS proteins
4. Conversion of PIP2 to PIP3
5. Glut4 receptors transported to the cell membrane
6. Phosphorylation of phosphinositide 3-kinase (PI-3K)
7. Activation of PIP3-dependent protein kinase B (PDK1)
8. Activation of insulin receptor tyrosine kinase

The correct insulin pathway is described as under:

2. Binding of insulin to the alpha subunit of the insulin receptor

8. Activation of insulin receptor tyrosine kinase

3. Phosphorylation of IRS proteins

6. Phosphorylation of phosphinositide 3-kinase (PI-3K)

4. Conversion of PIP2 to PIP3

7. Activation of PIP3-dependent protein kinase B (PDK1)

5. Glut4 receptors transported to the cell membrane

Explanation:

The insulin signaling pathway is described as under:

RTK (receptor tyrosine kinases) which is a receptor for insulin is an extracellular receptor but in contrast to other cell surface receptors it is catalytic in nature. In the absence of insulin (ligand), it is monomeric but as soon as it gets activated (activation occurs upon ligand binding), it undergo dimerization. It leads to auto-phosphorylation in it's tyrosine residue which subsequently leads to phosphorylation of tyrosine residue of other receptors. Such hyper-phosphorylated receptor have high affinity with enzyme/molecule like IRS protein which have SH2 domain . IRS down stream activates phosphinositide 3-kinase (PI-3K). This enzyme converts component of animal cell membrane PIP2 into PIP3. PIP3 also remains membrane bound but it has the potential to phosphorylate another enzyme named as PIP3-dependent protein kinase B (PDK1). Further, PDK1 leads to the activation of Akt or PK-B. Akt is a serine-threonine kinase which ultimately leads to the recruitment of Glut4 receptors on cell membrane for uptake of more and more glucose into the cell.

Note: Apart from this Akt also phosphorylates another protein named as FOXO which ultimately causes cell growth, Akt can also phosphorylate BAD protein so as to restrict cell apoptosis or we can say it leads to cell survival, Akt also leads to translation in a cell with the help of mTOR raptor etc.  

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