Hierarchical Disabled-1 Tyrosine Phosphorylation in Src family Kinase Activation and Neurite Formation
Hierarchical Disabled-1 Tyrosine Phosphorylation in Src family Kinase Activation and Neurite Formation
There are two developmentally regulated alternatively spliced forms of Disabled-1 (Dab1) in the chick retina: an early form (Dab1-E) expressed in retinal precursor cells and a late form (Dab1-L) expressed in neuronal cells. The main difference between these two isoforms is the absence of two Src family kinase (SFK) recognition sites in Dab1-E. Both forms retain two Abl/Crk/Nck recognition sites implicated in the recruitment of SH2 domain-containing signaling proteins. One of the Dab1-L-specific SFK recognition sites, at tyrosine(Y)-198, has been shown to be phosphorylated in Reelin-stimulated neurons. Here, we use Reelin-expressing primary retinal cultures to investigate the role of the four Dab1 tyrosine phosphorylation sites on overall tyrosine phosphorylation, Dab1 phosphorylation, SFK activation and neurite formation. We show that Y198 is essential but not sufficient for maximal Dab1 phosphorylation, SFK activation and neurite formation, with Y232 and Y220 playing particularly important roles in SFK activation and neuritogenesis, and Y185 having modifying effects secondary to Y232 and Y220. Our data support a role for all four Dab1 tyrosine phosphorylation sites in mediating the spectrum of activities associated with Reelin-Dab1 signaling in neurons.
- Cross Cancer Institute Canada
- University of Alberta Canada
- Cross Cancer Institute Canada
Extracellular Matrix Proteins, Cell Adhesion Molecules, Neuronal, Recombinant Fusion Proteins, Green Fluorescent Proteins, Nerve Tissue Proteins, Chick Embryo, Antibodies, Avian Proteins, Enzyme Activation, Gene Expression Regulation, Receptors, LDL, Enzyme Induction, Neurites, Animals, Humans, Protein Isoforms, Phosphorylation, Phosphotyrosine, Cells, Cultured, HeLa Cells
Extracellular Matrix Proteins, Cell Adhesion Molecules, Neuronal, Recombinant Fusion Proteins, Green Fluorescent Proteins, Nerve Tissue Proteins, Chick Embryo, Antibodies, Avian Proteins, Enzyme Activation, Gene Expression Regulation, Receptors, LDL, Enzyme Induction, Neurites, Animals, Humans, Protein Isoforms, Phosphorylation, Phosphotyrosine, Cells, Cultured, HeLa Cells
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