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Wss1 and STUbL pathways may direct substrates to different downstream degradation events, orchestrated by different Cdc48 complexes.
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Redox imbalance under certain conditions and in engineered strains may contribute to incomplete substrate utilization and may direct fermentation products to undesirable overflow metabolites.
Analysis of the S1-binding pockets of the various families also reveals a conserved aromatic residue on (H L5 (see Figure 2), which forms hydrophobic contacts with the bound inhibitors (see Supplementary Figure S1) and may be important for directing substrates into the S1 pocket.
This diversity in observed subcellular localisation patterns demonstrates that each B" subunit may direct the phosphatase to distinct sites and substrates within the cell.
The above mentioned PIPs bind actin through the amino acids Arg Pro Glu Leu and may direct PPP1 to a panoply of actin-associated substrates.
Some decisive elements may also serve in maintenance of catalytic competence via their action as gatekeepers directing substrate access/positioning or stabilizers of the heme environment enabling dioxygen activation.
It is possible that α-tubulin may be a direct substrate of ICP0's E3 ligase activity, but the history of ICP0 research suggests that such speculation is premature.
It has recently been suggested that the structural fold rather than the sequence may be the determining factor for PINK1 recognition of direct substrates (Wauer et al, 2015).
For example, p38 may regulate jun transcription via MEF2 and ATF2, two direct substrates of p38, whereas fos and egr-1 can be regulated by other p38 substrates, such as ternary complex factors (TCFs) [ 1, 2, 4].
We identify the target tyrosine residues in the cytoplasmic domain of FLRT1 and show that these are not direct substrates for Src kinase suggesting that the SFK may exert effects via potentiation of FGFR1 kinase activity.
Biochemically, P450s (cytochrome P450 monooxygenases) provide direct substrates or precursors of substrates for C20-GA2ox, so the presence of C20-GA2ox may be a prerequisite for the presence of the GAox family.
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