Glucose-induced inactivation of isocitrate lyase in Saccharomyces cerevisiae is mediated by the cAMP-dependent protein kinase catalytic subunits Tpk1 and Tpk2

Glucose-induced inactivation of isocitrate lyase (Icl) has been related to protein phosphorylation. Moreover, since rapid reversible inactivation preceded irreversible inactivation of the enzyme, phosphorylation was proposed as the triggering reaction that makes the enzyme accessible to the proteolytic machinery. The protein kinase involved in the process is unknown at the moment. In this work we demonstrate that Tpk1 and Tpk2, the catalytic submits of cAMP-dependent protein kinase, are involved in the signalling of short-term and long-term inactivation processes of Icl. We also demonstrate that threonine 53 is involved in a regulatory mechanism necessary for shortterm reversible inactivation of Icl, probably mediated through its phosphorylation. Other, as yet unidentified, residues are likely to be the target of distinct protein kinases mediating the irreversible long-term inactivation of Icl.