This year marks the 30th anniversary of the first reports of the phosphorylation of tyrosyl residues in proteins involved in signal transduction by Tony Hunter and his colleagues [1, 2]. Developments from this groundbreaking discovery have revealed remarkable insights into the regulation of signal transduction in response to growth factors, hormones and cytokines. Furthermore, our understanding of how such signalling events are disrupted in disease has provided the foundation for new therapeutic strategies that are at the core of current approaches to treating major diseases, such as cancer. Although the focus of research was originally on the kinases, the first characterization of the protein tyrosine phosphatases (PTPs) as a novel class of signalling enzymes over 20 years ago [3, 4] helped to establish that the coordinated regulation of the activities of both protein tyrosine kinases (PTKs) and phosphatases lies at the heart of control over signal transduction. Although to a certain extent there remain kinase and phosphatase camps, such a categorization of research is somewhat artificial. Nowadays we are in the fortunate position of being able to study the fundamental importance of reversible phosphorylation, using kinases and phosphatases as complementary perspectives from which to address major problems in biology.  In this Virtual Issue of FEBS Journal, I have selected some of the reviews and primary papers that have been published on this area of research in the journal since 2007. They cover various aspects of the importance of reversible tyrosine phosphorylation, and the regulation of protein tyrosine kinases and phosphatases, as well as the application of this knowledge to new approaches to therapeutic intervention. The Editorial Board of FEBS Journal encourages submission of more manuscripts in this area.

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References

1. Hunter, T. and Sefton, B.M. (1980) Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc. Natl. Acad. Sci. USA 77: 1311-1315.

2. Sefton, B.M., Hunter, T., Beemon, K. and Eckhart, W. (1980) Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell 20: 807-816.

3. Tonks, N.K., Diltz, C.D. and Fischer, E.H.  (1988) Purification of the major protein tyrosine phosphatases of human placenta.  J. Biol. Chem. 263: 6722-6730.
     
4. Tonks, N.K., Diltz, C.D. and Fischer, E.H.  (1988) Characterization of the major protein tyrosine phosphatases of human placenta.  J. Biol. Chem. 263: 6731-6737.

Review Articles

Protein tyrosine phosphatases: functional inferences from mouse models and human diseases (275, p 816-830)
Wiljan J. A. J. Hendriks, Ari Elson, Sheila Harroch, Andrew W. Stoker

Protein tyrosine phosphatases: regulatory mechanisms (275, p 831-847)
Jeroen den Hertog, Arne Östman, Frank-D. Böhmer

Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease (275, p 848-866)
Rafael Pulido and Rob H. van Huijsduijnen

Protein tyrosine phosphatases: structure–function relationships (275, p 867-882)
Lydia Tabernero, A. Radu Aricescu, E. Yvonne Jones, Stefan E. Szedlacsek

Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer (277, p 301-308)
Tetsuya Mitsudomi, Yasushi Yatabe

Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapy (277, p 309-315)
Isamu Okamoto

EGF receptor in relation to tumor development: molecular basis of responsiveness of cancer cells to EGFR-targeting tyrosine kinase inhibitors (277, p 316-326)
Kenji Takeuchi, Fumiaki Ito

Human anti-ErbB2 immunoagents – immunoRNases and compact antibodies (276, p 1527-1535)
Claudia De Lorenzo, Giuseppe D'Alessio

Calmodulin-mediated regulation of the epidermal growth factor receptor (277, p 327-342)
Pablo Sánchez-González, Karim Jellali, Antonio Villalobo

A decade of Cdc14 – a personal perspective (275, p 5774-5784)
Angelika Amon

Original Articles

Mitogen-activated protein kinase phosphatase-1 modulated JNK activation is critical for apoptosis induced by inhibitor of epidermal growth factor receptor-tyrosine kinase (276, p 1255-1265)
Kenji Takeuchi, Tomohiro Shin-ya, Kazuto Nishio, Fumiaki Ito

Mutation of epidermal growth factor receptor is associated with MIG6 expression (276, p 5239-5251)
Takeshi Nagashima, Ryoko Ushikoshi-Nakayama, Atsushi Suenaga, Kaori Ide, Noriko Yumoto, Yoshimi Naruo, Kaoru Takahashi, Yuko Saeki, Makoto Taiji, Hiroshi Tanaka, Shih-Feng Tsai, Mariko Hatakeyama

Differential binding of human immunoagents and Herceptin to the ErbB2 receptor (275, p 4967-4979)
Fulvia Troise, Valeria Cafaro, Concetta Giancola, Giuseppe D'Alessio, Claudia De Lorenzo

The localization of FGFR3 mutations causing thanatophoric dysplasia type I differentially affects phosphorylation, processing and ubiquitylation of the receptor (274, p 3078-3093)
Jacky Bonaventure, Linda Gibbs, William C. Horne, Roland Baron

The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1 (275, p 207-217)
Marie K. Inder, Lyn M. Wise, Stephen B. Fleming, Andrew A. Mercer

FLIP and MAPK play crucial roles in the MLN51-mediated hyperproliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis (275, p 3546-3555)
Ju-Eun Ha, Young-Eun Choi, Jinah Jang, Cheol-Hee Yoon, Ho-Youn Kim, Yong-Soo Bae

Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle (276, p 4102-4118)
Nikolai P. Kaimachnikov, Boris N. Kholodenko

Catalytically active membrane-distal phosphatase domain of receptor protein-tyrosine phosphatase α is required for Src activation (277, p 1562-1570)
Andrei M. Vacaru, Jeroen den Hertog

Phosphorylation of cyclin dependent kinase 4 on tyrosine 17 is mediated by Src family kinases (275, p 3099-3109)
Nicholas G. Martin, Peter C. McAndrew, Paul D. Eve, Michelle D. Garrett

NF-κB regulates the transcription of protein tyrosine kinase Tec (276, p 6714-6724)
Liang Yu, Oscar E. Simonson, Abdalla J. Mohamed, C. I. Edvard Smith

Interactions between the Fyn SH3-domain and adaptor protein Cbp/PAG derived ligands, effects on kinase activity and affinity (275, p 4863-4874)
Silje A. Solheim, Evangelia Petsalaki, Anne J. Stokka, Robert B. Russell, Kjetil Taskén, Torunn Berge

Differential membrane compartmentalization of Ret by PTB-adaptor engagement (275, p 2055-2066)
T. K. Lundgren, Moritz Luebke, Anna Stenqvist, Patrik Ernfors

Proteolytic processing of the receptor-type protein tyrosine phosphatase PTPBR7 (274, p 96-108)
Gönül Dilaver, Rinske van de Vorstenbosch, Céline Tárrega, Pablo Ríos, Rafael Pulido, Karlijn van Aerde, Jack Fransen, Wiljan Hendriks

Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells (275, p 69-88)
Yi-Wei Lou, Yi-Yun Chen, Shu-Fan Hsu, Ren-Kun Chen, Chih-Lei Lee, Kay-Hooi Khoo, Nicholas K. Tonks, Tzu-Ching Meng

Calpain-mediated degradation of reversibly oxidized protein-tyrosine phosphatase 1B (276, p 5622-5633)
Antje Trümpler, Bernhard Schlott, Peter Herrlich, Peter A. Greer, Frank-D. Böhmer

Redox regulation of dimerization of the receptor protein-tyrosine phosphatases RPTPα, LAR, RPTPµ and CD45 (275, p 2597-2604)
Arnoud Groen, John Overvoorde, Thea van der Wijk, Jeroen den Hertog

DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine (275, p 6268-6280)
Anne Seifert, Lindsey A. Allan, Paul R. Clarke

Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation (276, p 6324-6337)
Nora Göckler, Guillermo Jofre, Chrisovalantis Papadopoulos, Ulf Soppa, Francisco J. Tejedor, Walter Becker

Myristoylation of the dual-specificity phosphatase c-JUN N-terminal kinase (JNK) stimulatory phosphatase 1 is necessary for its activation of JNK signaling and apoptosis (277, p 2463-2473)
Ulla Schwertassek, Deirdre A. Buckley, Chong-Feng Xu, Andrew J. Lindsay, Mary W. McCaffrey, Thomas A. Neubert and Nicholas K. Tonks

Analysis of EphA4 receptor tyrosine kinase substrate specificity using peptide-based arrays (275, p 2561-2573)
Neil Warner, Leanne E. Wybenga-Groot, Tony Pawson

Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases (276, p 4395-4404)
Tara L. Davis, John R. Walker, Abdellah Allali-Hassani, Sirlester A. Parker, Benjamin E. Turk, Sirano Dhe-Paganon

Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells (276, p 3269-3276)
Kazuya Terasawa, Atsuhiko Ichimura, Fumiaki Sato, Kazuharu Shimizu, Gozoh Tsujimoto

Epidermal growth factor receptor-regulated miR-125a-5p – a metastatic inhibitor of lung cancer (276, p 5571-5578)
Guofu Wang, Weimin Mao, Shu Zheng, Jingjia Ye