Reversible phosphorylation: a birthday tribute to Herb Tabor

Abstract

Herb Tabor was the Editor-in-Chief of the Journal of Biological Chemistry (JBC) spanning the years 1971-2010. This year, Herb turns 100. What do you give a person turning 100? Our answer to this question was to dedicate two of our favorite JBC papers to Herb. Both of these papers focus on reversible phosphorylation, which we briefly review. In addition, we delve into a new finding that centers around a novel family of secreted kinases, suggesting that there are many new and exciting discoveries yet to explore.

Keywords: cancer biology; phosphatase; phosphatase and tensin homolog (PTEN); phospholipid; phosphorylation; protein kinase A (PKA); secretion.

Figure 1.

Reversible phosphorylation governs many cellular processes. The kinases and phosphatases are composed of two large families of enzymes.

Figure 2.

Active site of PTPases. The thiol phosphate intermediate is universal in the catalytic mechanisms. The Cys residue forms a covalent bond with the phosphate. A key Arg residue interacts with the negative oxygen atoms on the phosphate. All members of the PTPase family use a similar reaction mechanism and the C(X)₅R catalytic signature motif. Nitrogen atoms (blue balls), carbon atoms (gray balls), oxygen atoms (red balls), sulfur atom (yellow ball), and phosphorus atom (orange ball) are shown.

Figure 3.

PTEN catalytic reaction. PTEN is one of a limited number of phosphatases that does not have a protein substrate. PTEN catalyzes the removal of a phosphate from the 3′-position of PtdIns(3,4,5)P₃.

Figure 4.

Novel family of secreted kinases. A, schematic diagram of a typical secreted kinase. These kinases have NH₂-terminal signal peptides as well as kinase domains located at their COOH termini. B, fjx family tree. Fam20A, Fam20B, Fam20C, Fjx, Fam198A, and Fam198B are shown.