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Basal and Src kinase‐mediated activation of the EphA2 promoter requires a cAMP‐responsive element but is CREB‐independent
Author(s) -
Du Xiaojian,
Baldwin Cindy,
Hooker Erika,
Glorion Pauline,
Lemay Serge
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23018
Subject(s) - creb , proto oncogene tyrosine protein kinase src , tyrosine kinase , tyrosine protein kinase csk , fyn , biology , microbiology and biotechnology , kinase , chemistry , cancer research , signal transduction , transcription factor , biochemistry , sh3 domain , gene
We have previously identified the EphA2 receptor tyrosine kinase as a potentially important injury‐responsive gene and a transcriptional target of Src kinase activity in renal ischemia‐reperfusion injury (IRI). In the present study, we confirmed, using EphA2 gene trap mice that the endogenous EphA2 promoter is strongly activated following renal IRI. We also examined in more detail the mechanisms responsible for Src kinase‐induced activation of the −2 kb human EphA2 promoter and found that the minimal Src‐responsive elements were contained in the −145 to +137 region of the human EphA2 gene. This region contains a canonical cAMP‐responsive element (CRE) that we found to be critical for both basal and Src kinase‐induced transcriptional activity. However, despite activation of the prototypical CRE‐binding factor CREB by the Src kinase Fyn, siRNA‐mediated knockdown of CREB had no significant impact on either basal or Fyn‐induced EphA2 promoter activity. Similarly, activation of CREB by the adenylate cyclase agonist forskolin failed to induce EphA2 promoter activation. Thus, Src kinase‐induced activation of the EphA2 promoter is CRE‐dependent but CREB‐independent. J. Cell. Biochem. 112: 1268–1276, 2011. © 2011 Wiley‐Liss, Inc.