Author: Arun Babukuttan
Babukuttan, Arun, 2025 Understanding the mechanism of IGF-1R ligand binding and activation, Flinders University, College of Medicine and Public Health
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This project set out to better understand how a protein called the insulin-like growth factor 1 receptor, or IGF-1R, actually works inside our cells. IGF-1R is really important—it helps control how our cells grow, divide, and survive. It’s especially active during childhood growth but also plays a role in tissue repair and even some cancers. Scientists already know quite a bit about how IGF-1R is activated, but there are still some pieces of the puzzle missing, especially about certain areas of the protein that may help it bind to its partners (IGF-I and IGF-II).
In this study, we focused on a specific part of the receptor known as the FnIII-I domain, which might act as a kind of secondary binding site. To test this idea, we made precise changes (mutations) to four amino acids that we thought might be important. We then inserted these modified genes into human cells that don’t normally produce IGF-1R and checked whether the receptor still worked when stimulated.
What we found was pretty exciting—mutations at three of these sites made the receptor less responsive to stimulation, and one of them nearly shut down activation completely. This tells us that these parts of the receptor are more important than we thought and likely help stabilize how the receptor binds to its ligands and switches “on.”
In simple terms, this research helps fill in the blanks about how IGF-1R functions, which is really valuable not just for understanding biology but also for designing better drugs in the future—especially for diseases where IGF-1R is overactive, like cancer.
Keywords: IGF-1R, IGF-I, IGF-II, Cancer, FnIII-I domain, Mutations, Low Affnity Binding Site, Expression, Activation, Breast Cancer, Prostate Cancer, HEK 293FT Double Knockout Cells
Subject: Medical Biochemistry thesis
Thesis type: Masters
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Prof. Briony Forbes