Figure 2

Signaling pathways involving PFKFB3. Numerous molecules are associated with PFKFB3 regulation. (1) Progestin, estradiol and hypoxia induce binding of the transcription factors PR, ER and HIF, respectively, to their responsive elements in the PFKFB3 promoter. Inflammatory cytokines and stress stimuli increase PFKFB3 production via the P38/MK2/SRF pathway. Serum and EGF function through the ERK1/2 (extracellular-signal-regulated kinase)/RSK1–4 (ribosomal S6 kinase) pathway, and progestin also regulates glycolysis through this pathway as a secondary mechanism. (2) MiR-206 and miR-26b inhibit PFKFB3 by interacting with 3′UTR of PFKFB3 mRNA. Other negative regulators of PFKFB3, such as ubiquitin ligase APC/C-Cdh1 and SCF, catalyze the degradation of the PFKFB3 protein, which in turn results in decreased glycolysis in cells. (3) PFKFB3 is phosphorylated at Ser⁴⁶¹ within the C-terminal region by MK234, AMPK38, PKA and PKC.