Inhibitor-insensitive kinase

Active Inhibitor-insensitive Kinase Mutants (Orthogonal Protein Kinases)... 

Figure 6.3 Schematic illustration of the generation of inhibitor-insensitive kinase mutants. The interaction of ATP-site competitors with kinase domains has been structurally characterized through the so-called Traxler model [10]. The part of the inhibitor that corresponds to the adenine ring binds to the hinge region of the kinase domain via H bonds. Next to the hinge region are the hydrophobic back pocket and the surface-exposed front pocket, which do not play a role in ATP binding. However, these pockets are extremely critical determinants in inhibitor binding, since the...

Staurosporine, a kinase inhibitor, also suppressed PAL transcription and enzymatic activation, which indicates that the phosphorylation of still unknown (transcription) factors happened in response to stimulation by pectic fragments. However, another staurosporine-insensitive but salicylic acid responding pathway led to the transcription of pathogenesis related (PR) genes [26]. 

De la Rosa, L.A., Vilarino, N., Vieytes, M.R., and Botana, L.M. 2001b. Modulation of thapsigargin-induced calcium mobilisation by cyclic AMP-elevating agents in human lymphocytes is insensitive to the action of the protein kinase A inhibitor H-89. Cell Signal 13, 441 49. 

In brain, a large number of particulate soluble proteins are phosphory-lated in the presence of Mg " -ATP and Ca +—calmodulin. These phosphorylations can be blocked by phenothiazines and do not occur in the presence of cAMP or cGMP. Furthermore, they are unaltered by the Walsh inhibitor, which is specific for the cAMP catalytic subunit. Hence, investigators have concluded that there is present in both particulate and soluble fractions of brain a Ca " -calmodulin-dependent protein kinase that is insensitive to cyclic nucleotides and that contains its own set of protein substrates. A few reports have appeared in the literature claiming purification of a calcium-calmodulin-dependent kinase from mammalian brain. The en-... 

In the Chinese hamster ovary cell line ts20, containing a thermosensitive ubiquitin-activating enzyme, El, Sachse et al. (2002) showed that this coat is predominantly present on early endosomes and has a characteristic bilayered appearance in the electron microscope. The coat contains clathrin heavy as well as light chain, but lacks the adaptor complexes API, AP2, and AP3, by which it differs from clathrin coats on endocytic vesicles and recycling endosomes. The coat is insensitive to short incubations with brefeldin A, but disappears in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin. 

The brassinosteroid signal transduction pathway is given in Fig. 22.8. In Arabidopsis, BR binds with brassinosteroid insensitive 1 (BRIl) receptor and induces its autophosphorylation and dissociation from BRIl kinase inhibitor (BKIl). Active BRIl forms a heterodimer with BRIl-sssociated receptor kinase 1 (BAKl) and phosphorylates BR-signaling kinase 1 (BSKl) and constitutive differential... 

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