High impact information on Map3k3

• Map3k3 disruption did not alter the expression of the genes encoding Vegf-1, angiopoietin or their receptors [1].
• The development of embryonic, but not maternal, blood vessels in the placentas of Map3k3-/- embryos was impaired, revealing an intrinsic defect in Map3k3-/- endothelial cells [1].
• Map3k3-/- embryos died at approximately embryonic day (E) 11, displaying disruption of blood vessel development and the structural integrity of the yolk sac [1].
• Through its ability to bind actin, relocalize to Rac-containing membrane ruffles and its obligate requirement for p38 activation in response to sorbitol, we have termed this protein osmosensing scaffold for MEKK3 (OSM) [2].
• Taken together, these studies suggest a mechanism whereby RIP1 may mediate the p38 MAP kinase response to TNF-alpha, by recruiting the MAP3K MEKK3 [3].

Biological context of Map3k3

• Together, these results suggest an involvement of the MEKK3 kinase in negative regulation of cell cycle progression, and they provide the first insights into biologic activities of this kinase [4].
• It is demonstrated here that the MEKK3 kinase inhibits cell proliferation, a biologic response not commonly associated with members of the MAP3K family of kinases [4].
• We determined that angiotensin II induced MEKK3 phosphorylation [5].
• In contrast, small interference RNA directed against MEKK3 and a dominant negative form of MEKK3 caused the reduction of NFAT activation in response to angiotensin II in cardiac myocytes [5].

Anatomical context of Map3k3

• A conditionally activated form of MEKK3 stably expressed in fibroblasts arrests these cells in early G1 [4].
• The essential role of MEKK3 signaling in angiotensin II-induced calcineurin/nuclear factor of activated T-cells activation [5].
• MEKK3 is essential for lipopolysaccharide-induced interleukin-6 and granulocyte-macrophage colony-stimulating factor production in macrophages [6].
• However, the function of MEKK3 in immune cells has not been studied because germ-line MEKK3 knockout mice are embryonically lethal between embryonic days 10 and 11 [6].
• Recently, we found that MEKK3 plays a critical role in interleukin-1 (IL-1) receptor and Toll-like receptor 4 signalling using established primary mouse embryonic fibroblast (MEF) cell lines [6].

Associations of Map3k3 with chemical compounds

• Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM) was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity [7].

Physical interactions of Map3k3

• MEKK3 interacts with the PA28 gamma regulatory subunit of the proteasome [8].

Other interactions of Map3k3

• Furthermore, in vitro assays indicated that PA28 gamma was a MEKK3 substrate [8].

References