MEK mitogen activated protein

MEK Mitogen-activated protein kinase/extracellular signal-regulated kinase... 

Destabilization of raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen activated protein kinase signaling pathway.Mo/. CellBiol. 16 5839—45... 

Ceramide-activated protein kinase (CAPK) is a proline-directed membrane-bound kinase capable of mediating the effects of ceramide on Rafl kinase in vitro. Kolesnick and co-workers have subsequently identified the kinase suppressor of Ras (KSR) as CAPK and a novel member of the Ras/Raf/MEK (mitogen-activated protein kinase) signaling pathway. Furthermore, it was suggested that ceramide activation of KSR could mediate the effects of TNFa on Rafl (Xing and Kolesnick, 2001). 

CDK, cyclin-dependent kinase ERK, extracellular signal-regulated kinase GRK, G protein receptor kinase JNK, Jun kinase MAP kinase, mitogen activated protein kinase MEK, MAP kinase and ERK kinases RSK, ribosomal S6 kinase, GSK, glycogen synthase kinase SAPK, stress-activated protein kinase SEK, SAPK kinase. 

Mitogen-activated protein kinase phosphatases are dual-function protein phosphatases. Just as the MAPK kinases (e.g. MEKs) are unique as dual-functioning kinases in that they phosphorylate MAPKs on threonine and tyrosine residues, there are unique dual-function ing protein phosphatases that reverse the phosphorylation and activation of MAPKs [43], Such MAPK phosphatases (MKPs) were first identified as a product of vaccinia virus (VH1) and later found in all eukaryotic cells. There are now numerous members of this VH1 family of dual-functioning protein phosphatases. 

Mitogenic effects are mediated through MEK/MAPK (mitogen-activated protein kinase) and changes in metabolic activity mainly via PI3K. 

MEK mitogen-activated or extracellular signal-regulated protein kinase... 

Figure 21.9 The mitogen-activated protein kinase cascade (MAP kinase cascade). The active protein Ras activates Raf by promoting its recruitment to a cell membrane. Through a series of phosphorylations MAP kinase is activated as follows MAP kinase kinase kinase (Raf) phosphorylates MAP kinase kinase which, in turn, phosphorylates MAP kinase, the final target enzyme. MAP kinase phosphorylates transcription factors for genes that express proteins involved in proliferation. Another nomenclature for the enzymes is also used raf is MEKK MAPKK is MEK and finally ERK is MAP kinase (ERK is the abbreviation for extracellular-signal-related kinase) For comparison, the reader is referred to the metabolic phosphorylase cascade, which is discussed in Chapter 12 (Figure 12.12).

The effects of insulin on transcription are shown on the left of the illustration. Adaptor proteins Crb-2 and SOS ( son of sevenless ) bind to the phosphorylated IRS (insulin-receptor substrate) and activate the G protein Ras (named after its gene, the oncogene ras see p.398). Ras activates the protein kinase Raf (another oncogene product). Raf sets in motion a phosphorylation cascade that leads via the kinases MEK and ERK (also known as MARK, mitogen-activated protein kinase ) to the phosphorylation of transcription factors in the nucleus. 

There are at least three major effector pathways that are activated by neurotrophic factor-Trk receptors. The best-characterized pathway is the extracellular-regulated kinase (ERK) cascade, which is regifiated by activation of Ras, a small membrane-bound G protein. Activation of Ras occurs when activated Trk receptor associates with adaptor proteins and a GTP exchange factor (see Russell and Duman 2002 for details). Ras in turn recruits and activates a serine threonine kinase, Raf, to the membrane resulting in the activation of ERK kinase (also referred to as MEK) and ERK (also known as mitogen activated protein kinase or MAPK). Activation of the Ras-Raf-MEK-ERK cascade can lead to regifiation of many celMar proteins, including ribosomal S6-kinase (RSK). 

Fig. 10.2. Components and activation of the ERK pathway. Ordering and specificity of protein kinases in the ERK pathway. ExtraceUular signals are registered via receptor tyrosine kinases and passed on to the Ras protein. Ras GTP activates protein kinases belonging to the group of MAPKK kinases (Raf kinases and MEEKs). The MAPKK kinases phosphorylate the downstream group of protein kinases, the MAPKKs at two Ser residues. The MAPKKs phosphorylate the MAPKs (ERKl and ERK2) at a Tyr and a Thr residue, and thus are classified as dual specificity kinases. MAPK mitogenic activated protein kinase ERK extracellularly regulated kinase MEK MAP/ERK kinase MAPKK MAPK kinase MAPKKK MAPKK kinase MEKK MEK kinase.

The proteins Raf-1, MEK, and ERK are members of three larger families, for which several nomenclatures are employed. ERK is a member of the MAPK family (mitogen-activated protein Ainases mitogens are signals that act from outside the cell to induce mitosis and cell division). Soon after discovery of the first MAPK, that enzyme was found to be activated by another protein kinase, which came to be called MAP kinase kinase (MEK... 

Lopez-Pedrera, C., Buendia, P., Cuadrado, MJ., Siendones, E., Aguirre, M.A., Barbarroja, N., Montiel-Duarte, C., Torres, A., Khamashta, M., and F. Velasco, 2006, Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-kappaB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-l/ERK pathway.Arthritis Rheum. 54(1) 301—11. 

M phase portion of mitotic cell cycle including mitosis and cytokinesis during which the cell separates the duplicated genome into two identical halves MAPK mitogen activated protein kinase MEK MAPK/ERK kinase MEKK MAPK/ERK kinase kinase... 

Hymenialdisins proved to be nanomolar inhibitors of G2 DNA damage checkpoint and of the protein kinases Chkl and Chk2 [56], mitogen-activated protein kinase 1 (MEK-1) [57], and of other kinases [58[ therefore, they could be valuable agents in cancer therapy. In addition, hymenialdisins have been show n to inhibit... 

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