Alterations in EGF-dependent proliferative and phosphorylation events in XXXX cell lines by a @entity669 kinase inhibitor.

@entity1 @entity470 @entity5 @entity957 @entity14383 @entity12079 @entity669 @entity26500
The @entity470 is overexpressed in @entity957 and the @entity470 has been proposed as a potential target for new therapeutic agents in this @entity5 type. We have utilized a tyrphostintype inhibitor of the @entity470 @entity669 kinase domain ( @entity26500 ) to study EGF-dependent proliferation and phosphorylation in two @entity1 @entity957 cell lines. There were selected on the basis that whereas both cell lines have a large number of EGF receptors, one is growth inhibited by EGF (A431) while the proliferation of the other cell line (B2A4) is stimulated by EGF. EGF induced receptor autophosphorylation in each of the two cell lines; however, the level of phosphorylation was greater in the A431 cells than in the B2A4 cells. The pattern of proteins phosphorylated in response to EGF was different in the two squamous cell lines. @entity26500 antagonized the EGF-dependent proliferation of B2A4 cells, but was unable to reverse the inhibitory effect of EGF on A431 cell growth. @entity26500 partially inhibited @entity470 autophosphorylation in both cell lines and completely inhibited the EGF-dependent phosphorylation of other cellular proteins, one of which co-migrated with @entity14383 kinase in both cell lines. Moreover, different dose-response relationships for the inhibition of phosphorylation of various proteins were observed in A431 versus B2A4 cells. As a substrate competitive inhibitor of the @entity470 @entity669 kinase, the primary mode of action of @entity26500 may be to prevent the association and/or phosphorylation of multiple specific substrates of the receptor in a fashion which may be cell line dependent. The precise relationship of these phosphorylation events to @entity12079 sensitivity remains to be established.
