Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene. [5] [6]
Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene. [5] [6]
The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protein with structural features similar to members of the non-receptor-type protein-tyrosine phosphatase family, and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The bacterially expressed and purified DUSP1 protein has intrinsic phosphatase activity, and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. [7]
DUSP1 has been shown to interact with MAPK14, [8] [9] MAPK1 [9] [10] and MAPK8. [9]
A mitogen-activated protein kinase is a type of protein kinase that is specific to the amino acids serine and threonine. MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis.
Mitogen Activated Protein (MAP) kinase kinase kinase is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP kinase. Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. MAPKKKs are stimulated by a large range of stimuli, primarily environmental and intracellular stressors. MAPKKK is responsible for various cell functions such as cell proliferation, cell differentiation, and apoptosis. The duration and intensity of signals determine which pathway ensues. Additionally, the use of protein scaffolds helps to place the MAPKKK in close proximity with its substrate to allow for a reaction. Lastly, because MAPKKK is involved in a series of several pathways, it has been used as a therapeutic target for cancer, amyloidosis, and neurodegenerative diseases. In humans, there are at least 19 genes which encode MAP kinase kinase kinases:
Mitogen-activated protein kinase 1, also known as ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.
Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.
Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.
Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.
Dual specificity phosphatase 6 (DUSP6) is an enzyme that in humans is encoded by the DUSP6 gene.
Mitogen-activated protein kinase kinase kinase 4 is an enzyme that in humans is encoded by the MAP3K4 gene.
Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the DUSP3 gene.
Dual specificity protein phosphatase 4 is an enzyme that in humans is encoded by the DUSP4 gene.
Dual specificity protein phosphatase 10 is an enzyme that in humans is encoded by the DUSP10 gene.
Dual specificity protein phosphatase 2 is an enzyme that in humans is encoded by the DUSP2 gene.
Dual specificity protein phosphatase 7 is an enzyme that in humans is encoded by the DUSP7 gene.
Dual specificity protein phosphatase 16 is an enzyme that in humans is encoded by the DUSP16 gene.
Dual specificity protein phosphatase 5 is an enzyme that in humans is encoded by the DUSP5 gene.
Mitogen-activated protein kinase 11 is an enzyme that in humans is encoded by the MAPK11 gene.
Dual specificity protein phosphatase 12 is an enzyme that in humans is encoded by the DUSP12 gene.
Dual specificity protein phosphatase 19 is an enzyme that in humans is encoded by the DUSP19 gene.
MAPK phosphatases (MKPs) are the largest class of phosphatases involved in down-regulating Mitogen-activated protein kinases (MAPK) signaling. MAPK signalling pathways regulate multiple features of development and homeostasis. This can involve gene regulation, cell proliferation, programmed cell death and stress responses. MAPK phosphatases are therefore important regulator components of these pathways.
Candidalysin is a cytolytic 31-amino acid α-helical amphipathic peptide toxin secreted by the opportunistic pathogen Candida albicans. This toxin is a fungal example of a classical virulence factor. Hyphal morphogenesis in C. albicans is associated with damage to host epithelial cells; during this process Candidalysin is released and intercalates in host membranes. Candidalysin promotes damage of oral epithelial cells and induces lactate dehydrogenase release and calcium ion influx. It is unique in the fact that it is the first peptide toxin to be identified in any human fungal pathogen.
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