Growth Factors in the Microenvironment

Protein growth factors and their receptors are expressed throughout the body and play fundamental roles in regulating cell growth and differentiation, making them highly attractive therapeutic targets. However, as many growth factors are closely related and their signaling pathways are often overlapping and redundant, supracellular activation is a fundamental biological mechanism that nature uses to regulate growth factor activity in specific tissues.

A Prime Example: Targeting of Transforming Growth Factor-Beta (TGFβ)

TGFβ1 is a growth factor that is first produced by cells in a precursor form known as a proform. The proform is processed by the cell into the mature growth factor and a propeptide. The cell then secretes a complex consisting of the mature growth factor in physical association with the propeptide. This complex is inactive or “latent,” and in 2011, the laboratory of Professor Timothy Springer at the Harvard Medical School and Boston Children’s Hospital discovered the structure of this complex and the molecular basis for how this inactive complex is activated supracellularly.

Normal activation of latent TGFβ via integrin binding

 

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