Functional diversity of FGF‐2 isoforms by intracellular sorting

Abstract
Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular medium where it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006.

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