When enzymes bind multiple substrates, such as dihydrofolate reductase (shown right), enzyme kinetics can also show the sequence in which these substrates bind and the sequence in which products are released.
As with ATM, this activation results in the phosphorylation of multiple substrates, such as Chk1 [ 25].
We demonstrate that ERK kinase directly interacts with and phosphorylates FBW7 at Thr205, which leads to the ubiquitination and proteosomal degradation of FBW7 itself and the elevation of multiple FBW7 substrates, such as c-Myc, thus facilitating the proliferation and survival of pancreatic cancer cells.
Macrophage elastase (MMP-12) is a member of the family of matrix metalloproteinases (MMPs) and is active against multiple extracellular protein substrates such as elastin.
The XtrD transporter was able to accept multiple sugars as substrates, such as glucose and xylose.
Once activated, AKT can phosphorylate multiple substrates and downstream effectors, such as mTOR family, caspase family, cell cycle protein family and nuclear factor- κB (NF- κB), which contribute collectively to promote cell proliferation, survival, metastasis and chemoresistance.
As these genes encode multiple membrane-bound transporters, substrates such as amino acids, oligopeptides, sugars, inorganic cations and anions, essential metals, biogenic amines, vitamins, nucleosides and ammonia can be transferred across membranes, which in turn accelerates intercellular communication and leads to more efficient cellular metabolism.
There are also many examples of enzymes capable of modifying multiple substrates [ 5- 9], including signalling proteins such as cyclin-dependent kinases [ 10, 11], and ubiquitin ligases [ 12].
The activated form can phosphorylate multiple substrates, including several translation initiation factors, such as eIF2A, eIF3F eIF2S1 and eEF2, impairing the recycling of these factors between successive rounds of initiation and leading to inhibition of translation, which eventually results in shutdown of cellular protein synthesis and a reduction in cell proliferation [ 42, 43].
Fes substrates such as cortactin and HS1 have multiple pTyr sites separated by spacers of a suitable length for such docking-dependent phosphorylation.
Notably, multiple S/T-rich degrons are also found in several other SPOP substrates, such as Puc and Ci.
