ATP-Dependent Stabilization of Fibroblast Growth Factor 2: A New Function of Extracellular ATP?
Authors: (Karsten Rose, Department of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany)
Abstract: The discovery of the adenosinetriphosphate (ATP)-molecule by Karl Lohmannn in 1929 paved the way for an in-depth understanding that ATP is the universal form of direct energy in the cell. The hydrolysis of one or two acid anhydride bonds between the phosphate groups provides 32.3 kJ/mol and 64.6 kJ/mol energy, respectively. For some decades an additional role of ATP apart from the function as energy source and the role as a phosphate donor of kinase reactions was unthinkable. In 1970, Geoffrey Burnstock postulated that ATP could function also as an extracellular signal in nerve-mediated response of muscle cells. First, his investigations were ridiculed and negated, today purinergic receptor signaling is one of the most competitive and important aspect in the field of signal transduction. Recently, another function of ATP has been postulated: extracellular stabilization of the fibroblast growth factor 2, FGF2 (Rose et al., 2010). FGF2 plays a pivotal role in many biological processes like cell proliferation, embryogenesis, wound healing and angiogenesis (Ornitz and Itoh, 2001). The proliferative effect of FGF2 on endothelial cells leads to the pro-angiogenic phenotype of this growth factor.One interesting feature of this growth factor is its short half-life period. The half-life period in aqueous solution ranges from a few minutes to a few hours (Caldwell et al., 2004). This relative instability of FGF2 could be compensated by binding to heparin or heparansulphate proteoglycanes (HSPGs), which can protect the growth factor from proteolytic digestion and thermal destabilisation (Sommer and Rifkin, 1989). Beside heparin and HSPGs some other stabilizers of FGF2 were identified, though most of them neither occurred nor possessed a physiological function in human cells or tissues (Kajio et al., 1992; Mi et al., 2006; Ni et al., 2007).