The RS domains of SR proteins are conserved, and the serine residues within these domains are targets of phosphorylation by multiple kinases, including SRPK1 [30] and SRPK2 [31], Clk/Sty [32], and DNA topoisomerase I [33].
In A compartment cells far from the A/P compartment border which receive no Hh signal, full-length Ci (Ci-155) is phosphorylated by multiple kinases including PKA, which leads to generate a C-terminally truncated form [18] [24].
Following on from this, we remark that several other TFs are indeed, like FOXO, regulated by multiple PTMs, including the tumour suppressor p53 (UNIPROT accession P04637 for the human protein), which can undergo modifications including phosphorylation (by multiple kinases including ATM/ATR), acetylation, methylation and ubiquitylation at least 17 sites [133].
Cabozantinib is a small molecule inhibitor of multiple kinases including KIT.
Multiple kinases, including PKA, cyclic GMP-dependent protein kinase (PKG), and protein kinase C (PKC), can regulate BK channel currents.
The phosphorylation of p27 on T198 can be directed by multiple kinases including AMPK [ 31], Akt [ 32], and Rsk1 [ 33].
In vitro studies of kinase-reduced mutants such as p.G466V, p.G466E and p.G596R, have also shown that activation of the CRAF/MEK/ERK cascade can be inhibited by MEK inhibitors or sorafenib, an inhibitor for multiple kinase including CRAF.
Loss of function mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin, leads to accelerated p21Ras activity and phosphorylation of multiple downstream kinases, including Erk and Akt.
In addition to the abovementioned GSK-3β, C/EBPβ is also targeted by multiple protein kinases including protein kinase A, calmodulin-dependent protein kinase, Erk-1/2, ribosomal protein S6 kinase, and CDK2 [44].
This cell cycle dependent phosphorylation occurs in the absence of DNA damage and is accomplished by multiple protein kinases including cyclin A/cdk2, cyclin E/cdk2, cyclin D/cdk4, and aurora-A [7].
Nintedanib is an inhibitor of multiple tyrosine kinases, including receptors for PDGF, fibroblast growth factor, and vascular endothelial growth factor.
