4 - TYROSINE KINASE RECEPTORS

Tyrosine kinase receptor structure

Single transmembrane domain, an extracellular ligand-binding site, and an intracellular part with tyrosine kinase activity

Tyrosine kinase receptor function

bind signals like growth factors outside the cell and start phosphorylation cascades inside the cell by adding phosphate groups to tyrosine residues

Tyrosine kinase receptor full activation

Two receptors must come together (dimerize) after binding their signal. This allows them to phosphorylate each other (autophosphorylation) on tyrosine residues, activating the receptor.

Other enzymes that may be activated or associated with the tyrosine kinase receptors

Phospholipase Cγ, PI 3-kinase, and adaptor proteins that link to Ras/MAPK signaling

Insulin receptor structure

A tetramer made of 2 alpha and 2 beta subunits. The alpha subunits are extracellular and bind insulin, and the beta subunits span the membrane and have tyrosine kinase activity. Unlike other tyrosine kinase receptors, it is already dimerized before binding insulin.

Insulin receptor effects

Insulin promotes glucose uptake, glycogen synthesis, protein and lipid synthesis, and cell growth. It also reduces blood glucose by stimulating glucose transporters (GLUT4) and regulating metabolism.

Ras in insulin receptors

a small GTP-binding protein that acts like a molecular switch. It becomes active with GTP and inactive with GDP. Active Ras triggers MAP kinase pathways that lead to cell growth, division, and differentiation.

General steps of the insulin receptor (4)

1.  Insulin binds receptor

2. Receptor autophosphorylates

3. IRS proteins are phosphorylated

4. Pathways diverge (e.g., PI3K, Ras/MAPK)

Signaling pathway for protein synthesis

Insulin → Receptor → IRS → PI3K → PIP3 → Akt/PKB → mTOR → ↑ Protein synthesis

Signaling pathway for glucose utilization

Insulin → Receptor → IRS → PI3K → PIP3 → Akt/PKB → ↑ GLUT4 translocation → ↑ Glucose uptake

Crosstalk between insulin receptors and other pathways

Can interact with growth factor and cytokine signaling pathways, sharing components like Ras or PI3K, which allows integrated control of metabolism and growth.