IGFBP stands for the insulin-like growth factor-binding protein. This is classified as a carrier protein, or membrane transport protein, which means it moves ions, molecules, and other proteins across a biological membrane. This particular carrier protein serves insulin-like growth factor one or IGF-I.
There are seven members of the IGFBP protein family; IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, and IGFBP7. While there are technically seven members of this family, the seventh member is not regarded as a carrier protein for IGF-1.
The IGFBP family functions to help increase the half-life of IGFs that circulate through all tissues. This includes the prostate as well. Different members of the family have specific functions, though most of them follow the same lines. IGFBP-3 is the most abundant protein and binds with 80% of all IGFs. Its functions include assisting with circulation, working in the extracellular environment, and also working inside cells too. It is the primary source of IGF transportation in the bloodstream.
The main functions of all IGFBP proteins are simply to bind with insulin-like growth factors. By doing this, they circulate around the bloodstream and interact with cell receptors. When a high affinity of IGFs is present in the circulation, they can be directed to specific targeted tissues. Here, they can promote things such as cell proliferation, growth, differentiation, and survival.
Mechanism & Interactions
IGFBP will primarily interact with IGF-1. Research shows that IGF-1 is bound to one of the six family members 98% of the time. When bound to the most common protein (IGFBP-3) IGF-1 will bind to a 1:1 molar ratio. Binding often takes place inside the liver, which is the site of insulin production. By binding here, it allows growth hormones to stimulate the liver, helping it to continually produce more IGF-1.
All IGF binding proteins are proteins classified with a structure of 24 to 45 kDa. The six insulin-like growth factor binding proteins that bind to IGF are 50% similar to one another in cell structure. They share half of each other homology and bing with IGF-I along with IGF-II.
It is found that IGFBP-1 to -6 are remarkably similar in their protein structure. Each one has three domains that are distinct to this family. These domains are the N-terminal, linker, and C-terminal.
The N-terminal is a region that’s rich in cysteine and includes various disulfide bonds. This is the site were IGF binding will occur.
The linker domain is found in the center of the cell structure and will vary greatly depending on the specific insulin-like growth factor-binding protein. It is thought that all members of this family only share a 15% similarity between them here.
The C-terminal is where secondary IGF binding residues are found. This region is also rich in cysteine, though it also contains a motif that helps bind heparin to the site, along with ALS and nuclear localization sequence.
All members of the insulin-like growth factor-binding protein family are commonly found adjacent to one another. They’re formed in a tail-to-tail sequence.