Group 1 is characterised by IL-6 innate inflammatory protein pattern, with IL-6 occupying a central node with multiple downstream protein interactions.
Since ASK1 is located upstream of the SEK1/MKK4-JNK/SAPK and MKK3/MKK6-p38 MKK3/MKK6-p38, we examined the activation of the multipathwaysstream protein kinases by Western blot using phospho-specific antibodies (JNK and p38).
The most important self-renewal signaling pathways include WNT/b-catenin, NOTCH, and Hedgehog, each of which has multiple downstream target proteins and genes.
24– 26 Similar to KRAS, activated Ral-GTP interacts with multiple downstream effector proteins including RalBP1, which promotes membrane ruffling and filopodia formation through Rac1 and CDC42, as well as receptor trafficking via endocytic regulation.
In response to DNA double-strand breaks, ATM phosphorylates multiple key downstream proteins including p53 and BRCA1/2, the most common sporadic and inheritable mutated genes in breast cancer [ 6], thereby orchestrating complex signaling pathways involved in cell cycle arrest, DNA repair, senescence and apoptosis [ 7].
The genome-wide mapping of OCT4, NANOG, and SOX2 has revealed that these proteins co-target multiple downstream genes [15] associated with many chromatin-associated activities and complexes [42], and these proteins form a regulatory network to control cell phenotypes.
Mouse models provide specific evidence for the interaction of HOXC6 with multiple downstream targets including bone morphogenic protein 7 (BMP7), fibroblast growth factor receptor 2 (FGFR2), and platelet-derived growth factor receptor α (PDGFRA) that promote PCa metastasis to the bone microenvironment [ 42].
PHR proteins function through multiple downstream signaling pathways.
GTP-bound Rho proteins interact with multiple downstream effectors to elicit a variety of cellular responses including cytoskeletal reorganization, gene transcription, cell cycle regulation, and vesicular traffic [ 24].
