UNC119A Decreases the Membrane Binding of Myristoylated c‐Src

Plasma membrane localization of myristoylated c‐Src, a proto‐oncogene protein‐tyrosine kinase, is required for its signaling activity. Recent studies proposed that UNC119 protein functions as a solubilizing factor for myristoylated proteins, thereby regulating their subcellular distribution and signaling. The underlying molecular mechanism by which UNC119 regulates the membrane binding of c‐Src has remained elusive. By combining different biophysical techniques, we have found that binding of a myristoylated c‐Src‐derived N‐terminal peptide (Myr‐Src) by UNC119A results in a reduced membrane binding affinity of the peptide, due to the competition of binding to membranes. The dissociation of Myr‐Src from membranes is facilitated in the presence of UNC119A, as a consequence of which the clustering propensity of this peptide on the membrane is partially impaired. By these means, UNC119A is able to regulate c‐Src spatially in the cytoplasm and on cellular membranes, and this has important implications for its cellular signaling.