Chimeric constructs containing the SH4/Unique domains of cYes can restrict the ability of Scr527F to upregulate heme oxygenase-1 expression efficiently

cSrc and cYes are the two most homologous members of the Src-family of nonreceptor tyrosine kinases. These kinases perform redundant signalling functions in cells; however, there is also evidence to support specificity in signalling. In this report, specificity in signalling between activated forms of the cSrc and cYes oncoproteins was examined at the level of downstream gene expression. Here, pp60C-src(527F) (Src(527F)) and chimeric constructs of Src(527F) containing combinations of the SH4/Unique/SH3/SH2 domains of cYes were generated to determine whether the individual modular domains of cSrc or cYes could direct distinct cellular signals leading to differential gene expression. A biased, differential display analysis approach was used to analyse changes in gene expression. The data indicate that Src(527F) is capable of upregulating heme oxygenase-1 (HO-1) in CEF cells at the level of transcription and protein expression. Chimeric constructs containing the SH4/Unique domains of cYes were less efficient in upregulating HO-1 expression. Activation of cSrc and expression of the HO-1 gene product are each induced under conditions of hypoxia. We hypothesize that activated cSrc can direct upregulation of HO-1 while activated cYes may be less efficient in stimulating signal transduction pathways that direct expression of HO-1. (C) 2000 Elsevier Science Inc. All rights reserved.