We have suggested a new step in fertilization involving Src tyrosine kinase activation by a lipid called phosphatidic acid (PA). Large-scale HPLC/ELSD quantification of lipids at fertilization (Petcoff et al. J Lipid Res 2365-78, 2008) suggests that production of PA through the action of phospholipase D has a role in fertilization. In an action that requires intact membrane rafts, PA activates Src tyrosine kinase, which then activates phospholipase C (PLC?) to produce IP3 and subsequent intracellular calcium release to induce fertilization in Xenopus laevis (Stith, Developmental Biology 401(2):188–205; Bates et al., Developmental Biology 386:165-180, 2014).
This work suggests a new path to cancer as PA is elevated and Src is hyperactivated in many forms of cancer. Based on our lipid-Src binding work, studies by Stuart McLaughlin (SUNY Stony Brook) and Miguel Pons (Univ of Barcelona), anionic lipids may bind to the SH4 domain, the ULBR and SH3 domains of Src to “loosen” the tight configuration of Src to lead to its activation. Support: NIH (HD065661) and the University of Colorado Denver Undergraduate Research Opportunity Program