10 Questions
The enzyme ______ was found to be activated by another protein kinase, which came to be called MAP kinase kinase.
MAPK
Kinases in the ______ and MAPKKK families are specific for Ser or Thr residues.
MAPK
MAPKKs (here, ______) phosphorylate both a Ser and a Tyr residue in their substrate, a MAPK.
MEK
______ phosphorylations are longer lived than tyrosine phosphorylations.
Serine and threonine
The enzyme ______ binds IRS-1 through the former’s SH2 domain.
phosphoinositide 3-kinase
When bound to ______, protein kinase B (PKB) is phosphorylated and activated by yet another protein kinase.
PIP3
The activated PKB then phosphorylates ______ residues on its target proteins, one of which is glycogen synthase kinase 3 (GSK3).
Ser or Thr
In its active, nonphosphorylated form, GSK3 phosphorylates ______ synthase, inactivating it and thereby contributing to the slowing of glycogen synthesis.
glycogen
In muscle, PKB triggers the movement of ______ transporters from internal vesicles to the plasma membrane, stimulating glucose uptake from the blood.
glucose
The cascade of protein phosphorylations initiated by ______ stimulates glycogen synthesis.
insulin
Study Notes
Insulin Signaling Pathway
- Phosphorylation of IRS-1 on Tyr residues triggers a signaling cascade that transduces the insulin signal to the cytosol and nucleus
- Grb2 binds to phosphorylated IRS-1 through its SH2 domain and recruits Sos to the complex
- Sos catalyzes the replacement of GDP with GTP on Ras, activating it
Ras and Downstream Kinases
- Activated Ras activates the protein kinase Raf-1, which phosphorylates and activates MEK
- MEK phosphorylates and activates ERK, a mitogen-activated protein kinase (MAPK)
- ERK phosphorylates and activates transcription factors such as Elk1, which regulates insulin-regulated genes
Receptor Enzymes
- Insulin receptor is a receptor enzyme with a ligand-binding domain on the extracellular surface and a protein kinase active site on the cytosolic side
- Insulin receptor phosphorylates Tyr residues in specific target proteins, including IRS-1
Insulin Receptor Activation
- Insulin binding to the receptor activates the Tyr kinase activity, leading to autophosphorylation of the receptor
- Autophosphorylation opens up the active site, allowing the receptor to phosphorylate other target proteins
MAPK Cascade
- ERK is a member of the MAPK family, which is activated by the MAPK kinase MEK
- MEK is phosphorylated and activated by the MAPK kinase kinase Raf-1
PI-3K and PKB Pathway
- Phosphoinositide 3-kinase (PI-3K) binds to phosphorylated IRS-1 and converts PIP2 to PIP3
- PIP3 binds and activates protein kinase B (PKB), which phosphorylates and activates target proteins
- Activated PKB phosphorylates and inactivates glycogen synthase kinase 3 (GSK3), promoting glycogen synthesis
- PKB also triggers glucose uptake in muscle by stimulating GLUT4 translocation to the plasma membrane
This quiz covers the process of IRS-1 phosphorylation and its role in insulin signaling. It explores the binding of Grb2 to IRS-1 and the subsequent signaling cascade. Test your understanding of the molecular interactions involved in insulin signaling.
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