In the Beginning, There Was Protein Phosphorylation

John M. Kyriakis

doi:10.1074/jbc.r114.557926

Abstract

The importance of reversible protein phosphorylation to cellular regulation cannot be overstated. In eukaryotic cells, protein kinase/phosphatase signaling pathways regulate a staggering number of cellular processes, including cell proliferation, cell death (apoptosis, necroptosis, necrosis), metabolism (at both the cellular and organismal levels), behavior and neurological function, development, and pathogen resistance. Although protein phosphorylation as a mode of eukaryotic cell regulation is familiar to most biochemists, many are less familiar with protein kinase/phosphatase signaling networks that function in prokaryotes. In this thematic minireview series, we present four minireviews that cover the important field of prokaryotic protein phosphorylation.

Highlights

The phenomenon of reversible protein phosphorylation was discovered Ͼ50 years ago by Edwin Krebs and Edmond Fischer and described in a series of classic papers published in this journal
The notion of a multistep protein kinase pathway triggered by the production of second messengers and inactivated by protein phosphatases set a paradigm for understanding signal transduction by protein phosphorylation cascades
Numerous protein kinase cascades have been described in the intervening years, including the MAPKs, the Akt and mTOR pathways, the NF-␬B pathway, the JAK/STAT pathway, and others

Summary

Introduction

The phenomenon of reversible protein phosphorylation was discovered Ͼ50 years ago by Edwin Krebs and Edmond Fischer and described in a series of classic papers published in this journal. All eukaryotic protein kinases contain a conserved phosphotransferase catalytic domain consisting of 12 conserved subdomains designated with Roman numerals (I–XII). A portion of subdomain VI contains a conserved motif (H164RDLKXXN171 in PKA) that includes an Asp residue that likely functions as a catalytic base.

Results

Conclusion