PUBLICATION
Fyn-dependent phosphorylation of PlexinA1 and PlexinA2 at conserved tyrosines is essential for zebrafish eye development
- Authors
- St Clair, R.M., Emerson, S.E., D'Elia, K.P., Weir, M.E., Schmoker, A.M., Ebert, A.M., Ballif, B.A.
- ID
- ZDB-PUB-171102-3
- Date
- 2017
- Source
- The FEBS journal 285(1): 72-86 (Journal)
- Registered Authors
- Keywords
- Fyn, Mass Spectrometry, Phosphorylation, Plexin, Semaphorin
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Binding Sites/genetics
- Eye/embryology
- Eye/metabolism*
- HEK293 Cells
- Humans
- Mutation, Missense
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Phosphorylation
- Proto-Oncogene Proteins c-fyn/metabolism*
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/metabolism*
- Sequence Homology, Amino Acid
- Signal Transduction/genetics
- Tyrosine/genetics
- Tyrosine/metabolism*
- Zebrafish
- PubMed
- 29091353 Full text @ FEBS J.
Citation
St Clair, R.M., Emerson, S.E., D'Elia, K.P., Weir, M.E., Schmoker, A.M., Ebert, A.M., Ballif, B.A. (2017) Fyn-dependent phosphorylation of PlexinA1 and PlexinA2 at conserved tyrosines is essential for zebrafish eye development. The FEBS journal. 285(1):72-86.
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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping