Phosphorylation of tubulin tyrosine ligase: a potential mechanism for regulation of alpha-tubulin tyrosination

Abstract

The tubulin tyrosination/detyrosination 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 PKC mediated phosphorylation of TTL inhibits its activity, thereby preventing tubulin tyrosination. Phosphorylation of TTL is predicted to occur in a postulated Mg(++)/-ATP binding fold, leading to inhibition of Mg(++)/ATP binding and TTL mediated catalysis. The implications of such control are also discussed.