Citation:
FEBS J. 2017 Nov 1. doi: 10.1111/febs.14313. [Epub ahead of print]
Abstract:
Plexins (Plxns) are semaphorin (Sema) receptors that play important signaling roles, particularly in the developing nervous system and vasculature. Sema-Plxn signaling regulates cellular processes such as cytoskeletal dynamics, proliferation, and differentiation. However, the receptor-proximal signaling mechanisms driving Sema-Plxn signal transduction are only partially understood. Plxn tyrosine phosphorylation is thought to play an important role in these signaling events as receptor and non-receptor tyrosine kinases have been shown to interact with Plxn receptors. The Src-family kinase Fyn can induce the tyrosine phosphorylation of PlxnA1 and PlxnA2. However, the Fyn-dependent phosphorylation sites on these receptors have not been identified. Here, using mass spectrometry-based approaches, we have identified highly-conserved, Fyn-induced PlxnA tyrosine phosphorylation sites. Mutation of these sites to phenylalanine results in significantly decreased Fyn-dependent PlxnA tyrosine phosphorylation. Furthermore, in contrast to wildtype human PLXNA2 mRNA, mRNA harboring these point mutations cannot rescue eye developmental defects when co-injected with a plxnA2 morpholino in zebrafish embryos. Together these data suggest that Fyn-dependent phosphorylation at two critical tyrosines is a key feature of vertebrate PlxnA1 and PlxnA2 signal transduction.
Epub:
Yes
Link to Publication:
http://onlinelibrary.wiley.com/doi/10.1111/febs.14313/abstract
Organism or Cell Type:
zebrafish
Delivery Method:
microinjection