Cytosolic pH: A conserved regulator of cell growth?

Abstract

Although target of rapamycin (TOR) kinase and Ras are central regulators of cell growth in yeast and mammals, the molecular mechanisms underlying their regulation by nutrients are still poorly understood. Interestingly, recent studies identified cytosolic pH as a critical regulatory signal for both pathways, which might have widespread implications for tumor cell biology.

Keywords: Ras/PKA; TORC1; cytosolic pH; growth control; nutrient sensing.

Figure 1.

Cytosolic pH links glucose metabolism to the regulation of cell growth. In yeast, carbon source availability regulates cytosolic pH through modulation of plasma membrane ATPase (P-ATPase) activity. Cytosolic pH acts as a signal to trigger phosphorylation of Sch9 by target of rapamycin complex 1 (TORC1) and Ras activity upstream of cAMP-dependent protein kinase A (PKA) via vacuolar ATPase (V-ATPase). Note that V-ATPase interacts with different GTPases at different cellular compartments (golgi and vacuole) to regulate Ras and TORC1 activity. See text for details.