User:Felix Peix/Sandbox 968
From Proteopedia
Human Serine/Threonine/Tyrosine – interacting protein (STYX) is a catalytically inactive phosphatase, which belongs to the family of dual-specificity phosphatases (DUSPs). It is catalytically inactive due to one mutation of a cysteine residue, which is essential for catalytic activity in normal phosphatases. Through regulation of ERK signalling STYX influences an array of ERK-dependent processes.
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Description
As aforementioned, STYX is classified into the family of dual-specificity phosphatases. This family contains apart from STYX several catalytically active members. In general, they are able to dephosphorylate serine, threonine and tyrosine residues. DUSPs in turn belong to the class I of the protein tyrosine phosphatases (PTPs)group. These class I protein tyrosine phosphatases all have in common that their catalytic mechanism is mainly dependent on a cysteine residue in the active site. This cysteine residue is part of a motif, which is conserved throughout all members of this phosphatase group. In STYX the catalytic cysteine at position 120 is mutated to glycine, which renders this phosphatase unable to catalyze the dephosphorylation of its substrates due to a single mutation (C120G). Hence, it is called a pseudophosphatase.
In general, phosphatases are designated as pseudophosphatases, if they contain one or several mutation(s) residues in conserved phosphatase domains which are thought to be essential for the catalysis. This definition is of theoretical nature: the catalytic inactivity of most pseudophosphatases is just predicted based on the sequence since the majority of this class of proteins is widely unexplored. Data on substrates and/or possible residual catalytic activity lack for the majority of these proteins. Nevertheless, recent data indicates several possible roles for pseudophosphatases in physiology and disease (Reiterer, Eyers et al.).
For the cellular functions of STYX, Reiterer, Fey et al. could show that it is predominantly localized in the nucleus where it interacts with the MAP kinases ERK1/2. In the nucleus, STYX competes with the catalytically active dual-specificity phosphatase 4 (DUSP4) for ERK binding and when bound to phosphorylated or dephosphorylated ERK it acts as a nuclear anchor for ERK1/2. Thereby ERK signalling is regulated by STYX. Depletion of STYX was shown to have several strong effects on ERK signalling including an increase in ERK activity and a fragmentation of the Golgi apparatus, which is mediated by the altered ERK activity. The Golgi fragmentation in turn affects Golgi polarization which is an important process in migrating cells. The ability to migrate is one of the major aspects of metastasizing cancer cells. Therefore a link to a role in metastasis is conceivable and some evidence suggests a potential role of STYX in metastasis as described in the following paragraph on the biological relevance of STYX.
Structure
-Ähnlichkeit zu DUSP, ähnliche Interaktion zu MAPK1 -Active Site -Tyrosine-phosphatase domain (Funktion?) -Liganden (Funktion?)
Biological Relevance
It is known that STYX is an important regulator of ERK signalling in the nucleus. ERK1/2 in turn play many roles within in the cell including proliferation and differentiation. ERK signalling is also involved in disease: in many types of cancer ERK signalling is hyperactivated, which leads to hyperproliferation. Therefore STYX could be also involved in this disease: It could be shown that STYX depletion causes Golgi fragmentation. When the Golgi apparatus is fragmented, the polarization of the cell before starting migration doesn't work properly anymore and as a result the migrating ability is impaired. The migrating ability of cancer cells is crucial in the process of metastasis, therefore a small role of STYX in this process seems to be conceivable. Indeed several pieces of evidence suggest a role for STYX in cancer.
