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Review
. 2014 May 1;6(5):a020644.
doi: 10.1101/cshperspect.a020644.

The genesis of tyrosine phosphorylation

Tony Hunter  1
Affiliations
Review

The genesis of tyrosine phosphorylation

Tony Hunter. Cold Spring Harb Perspect Biol. .

Abstract

Tyrosine phosphorylation of proteins was discovered in 1979, but this posttranslational modification had been "invented" by evolution more than a billion years ago in single-celled eukaryotic organisms that were the antecedents of the first multicellular animals. Because sophisticated cell-cell communication is a sine qua non for the existence of multicellular organisms, the development of cell-surface receptor systems that use tyrosine phosphorylation for transmembrane signal transduction and intracellular signaling seems likely to have been a crucial event in the evolution of metazoans. Like all types of protein phosphorylation, tyrosine phosphorylation serves to regulate proteins in multiple ways, including causing electrostatic repulsion and inducing allosteric transitions, but the most important function of phosphotyrosine (P.Tyr) is to serve as a docking site that promotes a specific interaction between a tyrosine phosphorylated protein and another protein that contains a P.Tyr-binding domain, such as an SH2 or PTB domain. Such docking interactions are essential for signal transduction downstream from receptor tyrosine kinases (RTKs) on the cell surface, which are activated on binding a cognate extracellular ligand, and, as a consequence, elicit specific cellular outcomes.

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Figures

Figure 1.
Figure 1.
The human kinome. Based on the catalog of human protein kinases compiled by Manning et al. (2002), an unrooted relatedness tree was constructed using the catalytic domain sequences of the 478 eukaryotic protein kinases (ePKs). The seven major branches of the kinome are indicated: AGC, CAMK, CMGC, TK, TKL, STE, and CK1. The ends of the branches representing individual kinases are labeled with the names of each protein kinase. The TK (tyrosine kinase) branch at the top of the tree has 90 members. The RTKs are present in four major branches: EPH, INSR/TRK/AXL, FGFR/PDGFR/CSF-1R, and EGFR. The atypical protein kinases, shown in the inset at the bottom left, fall into seven small families, which are either distantly related to the ePKs or else unrelated in sequence. (Illustration reproduced courtesy of Cell Signaling Technology, Inc., www.cellsignal.com.)
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