Suppression of tubulin tyrosine ligase activity through reversible phosphorylation: a mechanism for inhibition of α-tubulin tyrosinylation

Abstract

The tubulin tyrosinylation/detyrosinylation cycle is a well-established posttranslational modification, which is carried out by two enzymes: tubulin tyrosine ligase (TTL) and tubulin tyrosine carboxypeptidase (TTCP). In this paper, I present evidence suggesting that the cycle itself is under the hierarchical control of reversible phosphorylation and that proteinkinase C (PKC)-mediated phosphorylation of TTL inhibits its activity, thereby preventing tubulin tyrosinylation. Phosphorylation of TTL is postulated to occur in its presumed Mg ++-ATP binding fold, leading to inhibition of Mg ++/ATP binding and TTL mediated catalysis. The implications of such control are also discussed.