Androgen receptor–Proto-oncogene tyrosine-protein kinase Src (AR-Src) protein-protein interface (AR-Src PPI)

The Androgen receptor–Proto-oncogene tyrosine-protein kinase Src (AR-Src) protein-protein interface is a critical regulatory site where the androgen receptor (AR) physically associates with the SH3 domain of the Src tyrosine kinase (Migliaccio et al., 2000, EMBO J). This interaction is a hallmark of non-genomic androgen action, allowing AR to trigger rapid cytoplasmic signaling cascades, including the MAPK/ERK and PI3K/Akt pathways, without requiring nuclear translocation or DNA binding (Castoria et al., 2003, Cancer Res). In prostate cancer, particularly castration-resistant forms, this interface is often exploited to drive aggressive cell proliferation and survival despite low levels of circulating androgens (Migliaccio et al., 2005, Steroids). Therapeutic agents like the S1 peptide or peptidomimetics are designed to specifically disrupt this interface, thereby inhibiting the oncogenic non-genomic signaling while leaving the classical genomic functions of AR intact (Migliaccio et al., 2007, Cancer Res). This selectivity offers a potential advantage over traditional anti-androgens by reducing systemic side effects and overcoming certain mechanisms of drug resistance. Consequently, the AR-Src interface represents a promising target for precision oncology in hormone-dependent malignancies.

Other names

Androgen receptor-Src complexAR-Src interactionAR/Src interfaceAndrogen receptor-Src tyrosine kinase complex

Disruption of the physical interaction between the androgen receptor and the SH3 domain of Src kinase, preventing the activation of non-genomic signaling pathways such as MAPK/ERK.