Three stable configurations, it seems that the NLS is active only when the kinase is in the DFG Asp, the setup, which is stabilized by imatinib binding. K phosphorylation at one of these three tyrosines can The c-Met Signaling Pathway N lobe change immediately Asp from the DFG on the conformation and entered Ing and inhibits the function of the ANS. L beings Cha K ing hydroxyl side of these three tyrosines Can also inhibit the conformation of the N lobe of the NLS function. Regulation of BCR-ABL nuclear import of BCR-ABL FabD Since F-actin. Binding and co localized with actin filaments in cells, it was suggested that the BCR-ABL to F-actin is bound and not imported in the nucleus Tats Chlich we show here that the C-terminal mutations, including normal those helix 3 of FabD st Ren, SNA can restore function even under conditions where the ABL kinase is active and autophosphorylated BCR63.

However, we found that deletion of the helix 4 of FabD could release the function module MCB. Because spiral st 4 mutations Ren the function of F-actin-binding FabD these results show that F-actin-binding per se is not necessary for the inhibition of the function of the ANS. Instead, the C-terminal region au NLS outside 3, including normal Hedgehog Pathway integrity t of the helix 3 of the ABL kinase activation FabD BCR63 conformation required to induce a blocking function NLS. Taken together, adversely k Our results can by a model in which the conformation of the Kinasedom ne Folding of the C-terminal region, confinement Regulate Lich FabD NLS function Chtigen k Can be accommodated.

In Figure 8, which represents shown, but one of many m Resembled scenarios conformation-activated kinase autophosphorylation can one of three specific sites of tyrosine influence on the folding of the C-terminal region of the mask intact NLS three interactions with a propeller FabD third Imatinib associated kinase conformation caused about a change in the folding of the C-terminal region, which is not to mask the three MCB. The interaction between the N-lobe and FabD kinase conformation is also supported by the findings that mutations FabD may affect the sensitivity to imatinib kinase. K in the absence of three-dimensional structural data We can only imagine how FabD and range from 612 to 774 aa aa, the NLS NLS 2 and 3 contains lt Can influence the conformation of the kinase N lobe.

It seems that the disruption of helix 4 FabD k can Balance of the kinase N lobe conformations that move not bind imatinib and imatinib resistance caused by a mechanism that also requires sequences surrounding NLS2 and NLS Region 3 Accurate amplification Ndnis interactions between conformational Kinasedom Ne, the NLS region FabD latency Aufkl tion Dimensional structure of the ABL or BCR ABL protein full L Length. Experimental cell culture methods and reagents. The monkey kidney cell line COS1 cells