Figure 6: Y26 phosphorylation of PGAM1 is important for glycolysis and anabolic biosynthesis as well as cell proliferation and tumour growth. | Nature Communications

Figure 6: Y26 phosphorylation of PGAM1 is important for glycolysis and anabolic biosynthesis as well as cell proliferation and tumour growth.

From: Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation

Figure 6

(a) Generation of H1299 cells with stable knockdown of endogenous hPGAM1 and rescue expression of mPGAM1 WT or Y26F. (b) PGAM1 activity in rescue cells expressing mPGAM1 Y26F mutant was compared with that in control cells harbouring an empty vector or rescue cells expressing mPGAM1 WT, respectively, in the presence and absence of 2,3-BPG. (c–h) Glycolytic rate (c), oxidative PPP flux (d), NADPH/NADP+ ratio (e), RNA biosynthesis (f), lipogenesis (g) and intracellular ATP levels in the presence or absence of 100 nM oligomycin (h) were measured in rescue cells expressing mPGAM1 Y26F mutant, compared with those in control rescue cells of mPGAM1 WT. (i,j) Rescue expression of catalytically less active Y26F mutant attenuates H1299 cell proliferation (i), as well as tumour growth potential of H1299 cells in xenograft nude mice (j). (j; left) Dissected tumours (indicated by red arrows) in a representative nude mouse; expression and Y26 phosphorylation levels of PGAM1 or mPGAM1 proteins in tumour lysates are shown. (j; right) Cells expressing mPGAM1 Y26F show significantly reduced tumour formation in xenograft nude mice compared with cells expressing mPGAM1 WT (P-values were determined by the paired Student’s t-tests). The error bars represent mean values±s.d. from three independent experiments (*0.01<P<0.05; **P<0.01).

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