The role of dual‐specificity phosphatase 3 in melanocytic oncogenesis

Abstract

Protein Tyrosine Kinases (PTKs) are enzymes with a major regulatory role in a variety of biological processes. Their activity is counteracted by Protein Tyrosine Phosphatases (PTPs). The interaction of these two enzymatic groups reversibly modifies the transcriptional and posttranscriptional status of protein targets. This is responsible for regulating fundamental signal transduction pathways in physiological and pathological contexts. PTPs are divided into four classes based on their biochemical structure, with class I containing the subgroup of dual-specificity tyrosine phosphatases (DUSPs). The members of the large and heterogeneous subgroup of DUSPs have the property of dephosphorylating both tyrosine and serine/threonine residues of their target kinases. Based on their structure and homology between phosphatase domains, they are further subdivided into seven subgroups that include atypical DUSPs (A-DUSPs) and mitogen-activated protein kinase (MAPK) phosphatases (MKPs), among others. In particular, A-DUSPs are comprised of 19 proteins characterized by a small size (<27 kDa and/or <250 aa), which allows dephosphorylation not only of protein targets but also of non-peptidic substrates, such as phosphoinositides, mRNA or glycans. 1