Identifying signaling pathway responsible for SRC-3 serine 857 phosphorylation. A study in lung cancer cells

Abstract

Signal transduction mediated by protein kinases and phosphatases is complex and highly coordinated. The mitogen activated protein kinases (MAPKs) are key components that transduce extracellular stimuli to biological responses by a three-tier module. The biological functions of steroid receptor coactivator-3 (SRC-3), a coactivator of nuclear hormone receptors and numerous transcription factors, is regulated by multiple pathways involving the MAP kinase signaling cascades. The oncogenic SRC-3 protein is found to be overexpressed in multiple human cancers, such as breast, prostate and lung cancer, and is implicated in the regulation of multiple physiological and pathological functions. The upstream kinase of SRC-3 phosphorylation at S857 in vivo has yet to be found, although ERK3 has been reported to phosphorylate this site. Here, we investigate the association of the ERK3-MK5 pathway with SRC-3 phosphorylation at S857 residue in the human lung cancer cells H1299.