A critical evaluation of protein kinase regulation by activation loop autophosphorylation
- Max Perutz Labs, Vienna Biocenter Campus (VBC), Austria
- Medical University of Vienna, Center for Medical Biochemistry, Austria
Figures
Figure 1
Anatomy of a protein kinase.
(A) Basic anatomy of a protein kinase. Important elements in catalysis and regulation are highlighted in color: glycine-rich loop (green), αC helix (orange), αD helix (purple), αG helix (pink), …
Figure 2
Kinase inhibition in cis and trans.
(A) Inhibition of insulin receptor kinase (IRK) in cis. The activation loop (teal) of IRK adopts a conformation in which it prevents the binding of ATP and displaces the αC helix into an inactive …
Figure 3
Kinase activation in cis and trans.
(A) Activation of PKCι in cis. The C-terminal AGC-specific extension of the kinase domain activates PKC by inserting various short linear motifs into regulatory pockets on the surface of the kinase …
Figure 4
Interpreting biochemical evidence for cis and trans autophosphorylation.
(A) Common methods to assay autophosphorylation and their capacity to differentiate stoichiometric mono-phosphorylation (black), from sub-stoichiometric (blue) or super-stoichiometric (magenta) …
Figure 5
Interpreting kinetic evidence for cis- and trans-autophosphorylation.
(A) Kinases that do not dimerize can undergo autophosphorylation only in cis. These asymmetric reactions don’t require collision events and are limited only by their intrinsic catalytic rate. They …
Figure 6
Interpreting crystallographic evidence for kinase dimerization.
(A) Crystal lattice formation in crystals of the checkpoint kinase (Chk2) domain in complex with ADP. The unit cell contains six molecules (cyan, purple, pink), which form dimers on three twofold …
Figure 7
Tools to study kinase dimerization and autophosphorylation in solution.
Physical parameters that are measured by each technique are listed alongside the biological questions that can be addressed. Each technique is accompanied by a list of example studies in which the …
Figure 8
The enigma of autophosphorylation.
(A) Activation loop autophosphorylation requires the activity of the kinase before it is itself phosphorylated on its activation loop. Logic dictates that the autophosphorylation reaction must, …
