1.A.108. The Fibroblast Growth Factor 2 (FGF2) Family
Unconventional secretory proteins lack signal peptides and their export from cells is not affected by brefeldin A, an inhibitor of protein transport along the classical secretory pathway (Nickel 2010). Export can be mediated by direct translocation across plasma membranes of cytoplasmic proteins such as fibroblast growth factor 2 which can be modified by phosphorylation involving the Tec protein kinase (La Venuta et al. 2016) so that it inserts into membranes, creating oligomeric pores that are intermediates in the secretion process (see Nickel and Seedorf 2008 and TC# 9.A.48). Tyrosyl phosphorylation of FGF2 followed by association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) triggers formation of a lipidic membrane pore, essential for FGF2 secretion (Steringer et al. 2012). Formation of disulfide bridges is also essential for this process (Müller et al. 2015). The cytoplasmic domain of the Na+/K+ ATPase, ATP1A1 (α-subunit) may function as a direct interaction receptor for the process (Zacherl et al. 2015). Extracellular FGF2 is trapped by cell surface proeoglycans, and it then plays a role in tumor-indiced angiogenesis (La Venuta et al. 2015). Proteoglycans may also play a role in the secretion of the cytoskeletal Alzheimer's disease-associated tau protein (P10636; Pompa et al. 2017). Tau secretion correlated with tau phosphorylation and aggregation (Hannan et al. 2016).