Eberly College of Arts and Sciences
Microbiology, Immunology, and Cell Biology
Enhanced expression and activity of cSrc are associated with ovarian cancer progression. Generally, cSrc does not contain acti- vating mutations; rather, its activity is increased in response to signals that affect a conformational change that releases its auto- inhibition. In this report, we analyzed ovarian cancer tissues for the expression of a cSrc-activating protein, AFAP-110. AFAP-110 activates cSrc through a direct interaction that releases it from its autoinhibited conformation. Immunohistochemical analysis re- vealed a concomitant increase of AFAP-110 and cSrc in ovarian cancer tissues. An analysis of the AFAP-110 coding sequence revealed the presence of a nonsynonymous, single-nucleotide polymorphism that resulted in a change of Ser403 to Cys403. In cells that express enhanced levels of cSrc, AFAP-110403C directed the activation of cSrc and the formation of podosomes indepen- dently of input signals, in contrast to wild-type AFAP-110. We therefore propose that, under conditions of cSrc overexpression, the polymorphic variant of AFAP-110 promotes cSrc activation. Further, these data indicate a mechanism by which an inherited genetic variation could influence ovarian cancer progression and could be used to predict the response to targeted therapy.
Digital Commons Citation
Clump, David A.; Yu, Jing J.; Cho, YoungJin; Gao, Rui; Jett, John; Zot, Henry; Cunnick, Jess M.; Snyder, Brandi; Clump, Anne C.; Dodrill, Melissa; Gannett, Peter; Caod, James E.; Shurina, Robert; Figg, W Douglas; Reed, Eddie; and Flynn, Daniel C., "A Polymorphic Variant of AFAP-110 Enhances cSrc Activity12" (2010). Faculty & Staff Scholarship. 2755.
Zhu, M., Fitzgerald, E. F., Gelberg, K. H., Lin, S., & Druschel, C. M. (2010). Maternal Low-Level Lead Exposure and Fetal Growth. Environmental Health Perspectives, 118(10), 1471–1475. https://doi.org/10.1289/ehp.0901561