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PMID: 15254079 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Src family kinases are involved in EphA receptor-mediated retinal axon guidance.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 24 ·No. 28 ·2004-07-14 ·Pages 6248-57

Knöll B, Drescher U

Abstract

EphA receptor tyrosine kinases and their ephrin ligands play important roles in wiring of the developing nervous system. We have investigated here the function of Src family kinases (SFKs) in the retinotectal projection to dissect the signaling pathways by which EphA receptors control actin/microtubule rearrangements that underlie growth cone guidance and collapse. Both EphAs and SFKs are expressed broadly in retinal growth cones, and SFKs are recruited to EphA receptors after ephrinA stimulation. In the stripe and growth cone collapse assays we observe an abolition of EphA-mediated repulsion after inhibiting SFKs, either pharmacologically or enzymatically via electroporation-mediated overexpression of the SFK inhibitor Csk. In addition, we identify cortactin and the RhoGEF ephexin, which interact with EphA receptors in retinal axons, as targets of SFK-dependent tyrosine phosphorylation. In sum, our data suggest an important role of SFKs as downstream signaling molecules in EphA receptor-mediated repulsive axon guidance.

MeSH Terms
Animals CSK Tyrosine-Protein Kinase Cell Line Chick Embryo Cortactin Electroporation Enzyme Inhibitors/pharmacology Eye Proteins/antagonists & inhibitors,physiology Green Fluorescent Proteins/analysis,genetics Growth Cones/enzymology,physiology Guanine Nucleotide Exchange Factors/metabolism Humans Kidney Mice Microfilament Proteins/metabolism Optic Nerve/embryology,enzymology Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinases/genetics,physiology Receptors, Eph Family/physiology Recombinant Fusion Proteins/physiology Retinal Ganglion Cells/cytology,enzymology src-Family Kinases/antagonists & inhibitors,genetics,physiology
Chemicals
CTTN protein, human Cortactin Cttn protein, mouse Enzyme Inhibitors Eye Proteins Guanine Nucleotide Exchange Factors Microfilament Proteins NGEF protein, human Ngef protein, mouse Recombinant Fusion Proteins green fluorescent protein, Aequorea victoria Green Fluorescent Proteins Protein-Tyrosine Kinases Receptors, Eph Family CSK Tyrosine-Protein Kinase src-Family Kinases CSK protein, human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Knöll Bernd
Medical Research Council Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom.
Drescher Uwe
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0985-04.2004
Published
2004-07-14
Pages
6248-57
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6729544
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0985-04.2004 PMC Full Text View journal details
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