Insulin is a protein hormone that binds to the insulin receptor tyrosine kinase,
ID: 211443 • Letter: I
Question
Insulin is a protein hormone that binds to the insulin receptor tyrosine kinase, causing a downstream phosphorylation cascade. In muscle and liver cells, the insulin binding signal ultimately results in the cell increasing glycogen synthesis. (Remember that insulin is produced when you have just eaten and have high blood glucose levels. This is a good time to store part of that excess glucose as glycogen.)
The rate limiting enzyme of glycogen synthesis is Glycogen Synthase (GS). This protein is regulated by glycogen synthase kinase-3 (GSK3). When GSK3 is active, GS is inactive.
1. What does GSK3 do to GS? (1/2 pt) (Bold or circle the right answer)
A) It phosphorylates GS
B) It dephosphorylates GS
C) It can both phosphorylate and dephosphorylate GS
2. (1/2 pt) This means that GS is active when it is
A) Phosphorylated
B) Dephosphorylated
GSK3 is in turn regulated by Protein Kinase B (AKT… Yes, I realize the abbreviation looks nothing like the actual name…that’s just the way it is). When AKT is active, GSK3 is inactive.
3. (1 pt) This means that AKT
A) Activates GSK3 via phosphorylation
B) Inhibits GSK3 via dephosphorylation
C) Activates GSK3 via dephosphorylation
D) Inhibits GSK3 via phosphorylation
4. Complete the diagram below showing how AKT acts upon GSK3 and how GSK3 acts upon GS. (See examples we did in class)
A) (1 pt) For each line, complete with an arrowhead for activation or flat line for inhibition
AKT------------------------- GSK3--------------------- GS
B) (1 pt) Assuming this pathway is isolated (e.g. assume the diagram you drew above works like dominoes, with one enzyme acting upon the next and no other enzyme influencing the system), IN THE PRESENCE of glucose, circle or bold the appropriate setting (activated or inhibited) for AKT and GSK3 (GS is completed for you). *HINT* if you get stuck, look at your diagram above and work backwards!
AKT (activated or inhibited)
GSK3 (activated or inhibited)
GS (Activated or inhibited)
Explanation / Answer
1. The correct option is A.
Glycogen synthase kinase-3 is a serine/threonine kinase which phosphorylates target protein at serine or threonine residues. Phosphorylation leads to inactivation of target protein.
Dephosphorylation of protein is mediated by different kind of proteins known as phosphatases.
2. Correct option is B.
GS is active when GSK-3 is inactive. That means when GS is dephosphorylated.
3. Correct option is D.
Protein kinase-B inhibits the activity of GSK-3 by phosphorylating serine residue. By the way protein kinase-B is a serine/threonine kinase encoded by gene Akt and hence belong to the family of Akt.
4.
A. AKT------------------------- GSK3--------------------- GS
AKT inhibits GSK3 and GSK3 in turn inhibits GS.
B. In presene of glucose and as an isolated pathway it looks as below.
AKT------------------GSK3------------------GS
Bold letter in the pathway indicates that in presence of glucose that particular enzyme and reaction carried by it are inhibited.
AKT------------------GSK3------------------GS
Bold letter in the pathway indicates that in presence of glucose that particular enzyme and reaction carried by it are inhibited.
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