For a study, researchers sought to understand that the dynamics of SCF-triggered phosphorylation were lacking. The relationship between signaling modules and SCF-supported functions was also unclear. After isolating MCs from human skin, global phosphoproteomic changes were analyzed by LC-MS/MS and selectively validated by immunoblotting. YoPro was used to check MC survival, and BrdU incorporation was used to track proliferation. RT-qPCR was used to measure gene expression, and ELISA was used to measure cytokines. ERK1 and ERK2 knock-down were used in addition to pharmacological inhibitors. CIC translocation and degradation in nuclear and cytoplasmic fractions were investigated. Following RNA interference, the effect of CIC on KIT signaling and function was investigated. SCF regulated ≈5,400 of the ≈10,500 phosphosites studied. The MEK/ERK cascade was more strongly activated than STAT5>PI3K/Akt>p38>JNK. The comparison of MEK/ERK and PI3K support for basic programs (apoptosis and proliferation) revealed module equipotency. ERK was the most influential kinase in functional outputs (gene expression, cytokines). Skin MCs were found to produce OSM and LIF. Surprisingly, SCF induced massive phosphorylation of a protein not previously associated with KIT: CIC. Phosphorylation was followed by CIC’s cytoplasmic appearance and degradation, which was sensitive to protease inhibition but not proteasome inhibition. ERK was required for both shuttling and degradation. On the other hand, CIC-siRNA aided KIT signaling, functional outputs, and survival. The SCF/KIT axis was prominent in MCs, with MEK/ERK being the most prominent module. An inhibitory circuit connected KIT and CIC. CIC stabilization in MCs could be a therapeutic option for allergic and MC-driven diseases.
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