11245462 This pathway is stimulated by environmental and chemical stress as well as by exposure to cytokines, and it appears to play a role in the induction of apoptosis (10 , 11) . p38 MAPK is activated by hyperosmolarity and environmental stress and regulates pro- or anti-apoptotic effects in a stimulus and cell-type specific manner (12 , 13) . p38 MAPK is phosphorylated by either MKK3 (14) or MKK6 (15 , 16) .
8939929 B , graphical representation of p38 hog and SAPK activation in each cell line and in vector transfected G418-resistant control cells. [View Larger Version of this Image (39K GIF file)] MKK3-AL and MKK6-AL Expression Impair the Activation of p38 hog But Not SAPK MKK3 and MKK6 can phosphorylate p38 hog in vitro and have been proposed as potential physiologic p38 hog activators ( 18 , 19 , 20 ).
11732999 (CellType: chondrocyte) On the other hand, p38 MAPK is known to be a stress signal transducer, and phosphorylation of p38 MAPK in chondrocytes by EGF [ 25 ], PTH [ 41 ], and GDF-5 [ 42 ] regulates differentiation of chondrocytes. p38 MAPK is phosphorylated by MKK3, and MKK6 [ 45 ], and Atf-2 is one of the transcription factors downstream of p38 MAPK [ 31 ].
10716930 Since MKK3 does not bind to p38alpha or p38eta2, the selectivity of MKK3 in activating p38alpha MAPK is not caused by a difference in docking interactions of MKK3 with p38alpha and p38eta2.
11560921 SEK-1 and MKK-3/6 are known to phosphorylate p38 MAPK and SAPK/JNK, respectively ( 41-45 ); thus, we theorize that alpha-synuclein affects the phosphorylation of MAPKs by MAPKKs.
12589052 (CellLineName: COS I) Expression of Smad7 facilitates the interaction between MKK3 and p38 MAP kinase.
10593906 Both MKK3 and MKK6 are upstream kinases that can activate and phosphorylate p38 MAPK ( 25 , 26 ).
9430721 These data demonstrate that MKK3 and MKK6 differentially phosphorylate p38 MAP kinase isoforms.
9379049 (Tissue: marrow, CellType: macrophage)
MKK3 phosphorylates an unspecified isoform of p38. This interaction was modeled on a demonstrated interaction between human MKK3 and p38 from an unspecified species
8622669 (Organ: heart, Tissue: smooth muscle, CellType: cardiomyocyte, CellLineName: MB-231) In contrast, MKK3, MKK4, and MKK6 contribute to p38 MAPK activation caused by UV radiation.