Is activation of specific MEK-ERK cascade necessary for TGFbeta signaling and crosstalk with PKA and PKC pathways in cultured rat articular chondrocytes?
The results indicate that TGFbeta transduces a predominant signal pathway through MEK-ERK-Elk1, independent of MEKK1 or TAK1 pathway in CRAC. However, in HepG2, activation of MEKK1 and TAK1 is essential for TGFbeta-induced signal transmission. The results also demonstrated that in CRAC, MEK-ERK pathway activated by TGFbeta is negatively regulated by PKA cascade but transactivated by PKC.
The upregulation of proinflammatory factors during early presymptomatic stages as well as the expansion of immune activation as disease progresses in mutant SOD1 transgenic mice suggest that immune-inflammatory mechanisms could contribute to disease progression.