Chapter title |
The Extended Family of Protein Tyrosine Phosphatases
|
---|---|
Chapter number | 1 |
Book title |
Protein Tyrosine Phosphatases
|
Published in |
Methods in molecular biology, January 2016
|
DOI | 10.1007/978-1-4939-3746-2_1 |
Pubmed ID | |
Book ISBNs |
978-1-4939-3744-8, 978-1-4939-3746-2
|
Authors |
Andrés Alonso, Caroline E. Nunes-Xavier, Yolanda Bayón, Rafael Pulido, Alonso, Andrés, Nunes-Xavier, Caroline E., Bayón, Yolanda, Pulido, Rafael |
Abstract |
In higher eukaryotes, the Tyr phosphorylation status of cellular proteins results from the coordinated action of Protein Tyrosine Kinases (PTKs) and Protein Tyrosine Phosphatases (PTPs). PTPs have emerged as highly regulated enzymes with diverse substrate specificity, and proteins with Tyr-dephosphorylation or Tyr-dephosphorylation-like properties can be clustered as the PTPome. This includes proteins from the PTP superfamily, which display a Cys-based catalytic mechanism, as well as enzymes from other gene families (Asp-based phosphatases, His-based phosphatases) that have converged in protein Tyr-dephosphorylation-related functions by using non-Cys-based catalytic mechanisms. Within the Cys-based members of the PTPome, classical PTPs dephosphorylate specific phosphoTyr (pTyr) residues from protein substrates, whereas VH1-like dual-specificity PTPs dephosphorylate pTyr, pSer, and pThr residues, as well as nonproteinaceous substrates, including phosphoinositides and phosphorylated carbohydrates. In addition, several PTPs have impaired catalytic activity as a result of amino acid substitutions at their active sites, but retain regulatory functions related with pTyr signaling. As a result of their relevant biological activity, many PTPs are linked to human disease, including cancer, neurodevelopmental, and metabolic diseases, making these proteins important drug targets and molecular markers in the clinic. Here, a brief overview on the biochemistry and physiology of the different groups of proteins that belong to the mammalian PTPome is presented. |
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