In contrast to master regulators the so called mid-level regulators can not only be mediators of different incoming regulatory signals but also influence multiple downstream components or pathways.
For example, although a recent study has shown that EGFR is expressed at low levels in SCLC, (Tanno et al, 2004) our results indicate that the pathway is being activated by overexpression of multiple downstream components, potentially bypassing benefits that may be derived from EGFR-targeted therapy.
A prolonged stimulation with higher agonist concentrations can create non-selective membrane pores [16], or can stimulate multiple downstream signalling components, e.g. mitogen-activated protein kinases (MAPKs; ERK, p38, SAPK/JNK), Rho kinase and caspases leading to apoptosis/necrosis, and membrane blebbing, all involved in cell death [58].
Signals transduced through these components activate multiple downstream signaling cascades, inducing changes in cellular metabolism, gene expression, and cytoskeletal organization.
Compared to miR-21 and miR-10a that directly target IL-12 genes, some other miRNAs target the signaling components that will affect multiple downstream targets.
TAK1 also activates MAPK (mitogen-activated protein kinase) kinases that switch on p38 MAPKs and JNKs (c-Jun N-terminal kinases) [ 16, 17], whereas the canonical IKK complex has multiple downstream targets, including not only the inhibitory IκBα component of the transcription factor NF-κB, but also the inhibitory p105/NF-κB1 p105/NF-κB1f the Tpl2 (tumour progression locomponentnase.
Together, our results confirm that IGF-1R signaling incites multiple downstream cascades in which the key MAPK/ERK and PI3K/Akt components constitute the central signaling nodes that regulate IGF-1/IGF-1R signal-mediated proliferandon antiestrogenogen resistance in MCF7/IGF-1R cells.
These responses are likely induced by the pronounced downregulation of multiple Hsp90 protein clients, as well as their associated and downstream components, such as Cyclin D1, Cdk4, pRb, E2F1, IGF-IR, Akt, FOXOs, IKKs, NF-κB, cIAP1, Survivin, ERK1/2 and c-Met, resulting in cell cycle arrest, decline in cell motility and potent activation of Caspase-mediated apoptosis.
Rather, we focused more on the comparative transcriptome profiling of all these diverse upstream and downstream components of stress signaling cascade in response to multiple stresses (like salinity, drought, and cold, as well as exogenous ABA application, which mimics oxidative stress), between salt-sensitive and salt-tolerant rice varieties.
In addition, second messengers can have multiple downstream targets, thereby expanding the scope of signal transmission.
The arrows indicate activation of downstream components.
