The reasons for this are unknown but may relate to the complexities of the pathways regulated by p38, which is at the hub of the stress-induced response and regulates many downstream kinases and cellular processes [6].
ATM phosphorylates more than 700 proteins, including many downstream kinases (Matsuoka et al. 2007) demonstrating a broad range of functions.
In the presence of DSBs, ATM-dependent signaling is also involved in the regulation of the intra-S phase checkpoint through the activation of many downstream kinases.
In the complex molecular infrastructure that underlies the mechanisms of activation and transduction, ERK orchestrates a series of signalling events that result in the recruitment of many downstream factors, including kinases, transcription factors, and other proteins.
However, as each MAPK shares targets and functions with many upstream and downstream kinases and transcription factors, specificity of the pathways and their fiber type-specific role are not fully resolved.
This pathway is highly expressed in MM and shares many downstream targets with the Pim kinases which function in parallel, though independently.
Exposure to ROS leads to reversible oxidation of thiol groups of key cysteine residues in many downstream proteins, including transcriptional regulators, kinases, Rho and RAS GTPases, phosphatases, structural proteins, metabolic enzymes, and SUMO ligases.
Ras is a small GTPase that connects RTK activation to the triggering of many downstream effector pathways including MAP kinase cascades.
The AKT kinase has many downstream substrates involved in apoptosis, cell proliferation and protein synthesis, one of which is mTOR (mammalian target of rapamycin).
ALK rearrangements create an oncogenic ALK tyrosine kinase that activates many downstream signaling pathways resulting in increased cell proliferation and survival [ 1].
GTP-bound Rho proteins induce many downstream effects through interactions with an array of effector proteins, including protein kinases, lipid kinases, phospholipases, and various adaptor proteins.
