The tyrosine kinase Src boosts protein glycosylation by stimulating the transport of specific enzymes from the Golgi to the ER, Gill et al. reveal.
Src is activated downstream of growth factor receptors, but although a portion of the kinase localizes to the Golgi, little is known about its function at this organelle. Gill et al. discovered that growth factor stimulation induced a group of glycosylating enzymes called GalNac-Ts to relocate from the Golgi to the ER. This redistribution was blocked by inhibiting Src or by preventing the formation of COP-I transport vesicles. These vesicles only convey GalNac-Ts in response to Src activation: other glycosylation enzymes stayed put in the Golgi.
GalNac-Ts add N-acetylgalactosamine sugars to serine and threonine residues of secretory proteins—the initial step in the O-glycosylation pathway. Src activation and enzyme redistribution increased O-glycosylation levels, perhaps because ER-localized GalNac-Ts have access to their protein substrates for longer, or because they face less competition from other glycosylation enzymes that remain in the Golgi.
Senior author Frederic Bard now wants to understand how GalNac-Ts are specifically recruited into COP-I vesicles upon Src activation—he suspects that the kinase phosphorylates an adaptor protein that links the enzymes to the COP-I machinery. Another question is how increased O-glycosylation affects cell behavior. One possibility is that changing the glycosylation pattern of cell surface proteins will alter their interactions with neighboring cells or the extracellular matrix, suggesting a potential new way for growth factors and Src to influence cell adhesion.
