Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene. [5] [6]
Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene. [5] [6]
The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide variety of extra- and intracellular signals. As an essential component of the MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [7] MAP2K1 is altered in 1.05% of all human cancers. [8]
The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions. During meiosis double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-sister chromatid exchange, rather than by inter-homolog exchange. Molecular-level studies of recombination during budding yeast meiosis have shown that recombination events initiated by DSBs in regions that lack corresponding sequences in the homolog are efficiently repaired by inter-sister chromatid recombination. [9] This recombination occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of joint molecules.
MAP2K1 is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase that is thought to slow down, but not entirely block, sister chromatid recombination. Loss of MEK1 allows inter-sister DSB repair and also inter-sister Holliday junction intermediates to increase. Despite the normal activity of MEK1 in reducing inter-sister chromatid recombination, such recombination still occurs frequently during normal budding yeast meiosis (although not as frequently as during mitosis), and up to one-third of all recombination events are between sister chromatids. [9]
MAP2K1 has been shown to interact with C-Raf, [10] Phosphatidylethanolamine binding protein 1, [10] MAP2K1IP1, [11] [12] GRB10, [13] MAPK3, [12] [14] [15] [16] [17] MAPK8IP3, [18] [19] MAPK1 [10] [11] [20] [21] [22] [23] MP1, [12] and MAP3K1. [24]
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:
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. C-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases, from the TKL (Tyrosine-kinase-like) group of 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 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 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 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2.
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 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 mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.
Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the MAP3K11 gene.
14-3-3 protein theta is a protein that in humans is encoded by the YWHAQ gene.
Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with RPS6KA4, are thought to mediate the phosphorylation of histone H3, linked to the expression of immediate early genes.
Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.
C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene.
Mitogen-activated protein kinase kinase kinase 10 is an enzyme that in humans is encoded by the MAP3K10 gene.
Protein tyrosine phosphatase receptor-type R is an enzyme that in humans is encoded by the PTPRR gene.
MAP kinase-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPKAPK3 gene.
Mitogen-activated protein kinase scaffold protein 1 is a scaffold protein that in humans is encoded by the MAPKSP1 gene.
Dual specificity protein phosphatase 16 is an enzyme that in humans is encoded by the DUSP16 gene.
Mitogen-activated protein kinase 12, also known as extracellular signal-regulated kinase 6 (ERK6) or stress-activated protein kinase 3 (SAPK3), is an enzyme that in humans is encoded by the MAPK12 gene.
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