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

The tubulin tyrosination/detyrosination cycle is a well-established posttra nslational modification, which is carried out by two enzymes: Tubulin Tyros ine Ligase (TTL) and Tubulin Tyrosine Carboxypeptidase (TTCP). In this pape r, I present evidence suggesting that the cycle itself is under the hierarc hical control of reversible phosphorylation and that PKC mediated phosphory lation of TTL inhibits its activity, thereby preventing tubulin tyrosinatio n. Phosphorylation of TTL is predicted to occur in a postulated Mg++/-ATP b inding fold, leading to inhibition of Mg++/ATP binding and TTL mediated cat alysis. The implications of such control are also discussed. (C) 2000 Wiley -Liss, Inc.