The NOX system can be activated through several signaling pathways, including mitogen-activated protein kinases (MAPKs), protein kinase C (PKC), and Ca2+ (Myhre et al. 2009); thus, it is likely that different PCBs may stimulate different aspects of this pathway, resulting in final assembly of an active enzyme.
A further level of complexity in regard to the role of Bid in the response to genotoxic stress lies in the fact that Bid can be activated through several distinct mechanisms after DNA damage.
NF-kB can be activated through several kinases including IkB kinases (IKKs).
In mammals, CREB plays an important role in many biological processes [ 1] and can be activated through several signaling pathways (see reviews: [ 1, 3]).
Cyclooxygenase-2 can be activated through several cancer-associated biological pathways, such as Wnt- and Ras-related ones (Brown and DuBois, 2005).
It may be activated through several cellular mechanisms, including reducing BubR1 protein levels [ 11, 26, 27], increasing ER-α transcription [ 28, 29], activating RHO GTPase [ 30], MAPK and ElK1 [ 31], inducing MMP expression [ 32], and constitutive activation of ERK1/2 [ 19].
As CCND1 is activated through several mechanisms, it is not a specific indicator of WNT activation.
PLSCR1 has been shown to be engaged when cells are activated through several plasma membrane receptors, including the epidermal growth factor receptor and the high-affinity IgE receptor [30].
TGF- β1 and TGF- β3 can be activated through their interaction with several integrins, including alphavbeta5 [ 74, 76, 78, 87].
The canonical pathway can also be activated through the signaling of several G protein coupled receptors, IL1- and toll-like receptors and tumor necrosis factor receptor type 1 (TNFR1), whereas the rest of the TNFR family usually activates the non-canonical NFκB pathway, leading to the formation of transcriptionally active NFKB2/RELB heterodimers (14).
These two enzymes thus appear to be activated through the comprehensive effects of several activators with low specificities, physiologically, although it is possible that they have unknown activators with higher specificities.
