Sustained activation of N-WASP through phosphorylation is essential for neurite extension.

Neurite extension is a key process for constructing neuronal circuits during development and remodeling of the nervous system. Here we show that Src family tyrosine kinases and proteasome degradation signals synergistically regulate N-WASP in neurite extension. Src family kinases activate N-WASP through tyrosine phosphorylation, which induces Arp2/3 complex-mediated actin polymerization. ...
Tyrosine phosphorylation of N-WASP also initiates its degradation through ubiquitination. When neurite growth is stimulated in culture, degradation of N-WASP is markedly inhibited, leading to accumulation of the phosphorylated N-WASP. On the other hand, under culture conditions that inhibit neurite extension, but favor proliferation, the phosphorylated N-WASP is degraded rapidly. Collectively, neurite extension is regulated by the balance of N-WASP phosphorylation (activation) and degradation (inactivation), which are induced by tyrosine phosphorylation.
Mesh Terms:
Acetylcysteine, Actin-Related Protein 2, Actin-Related Protein 3, Amino Acid Sequence, Animals, COS Cells, Cell Line, Cercopithecus aethiops, Cysteine Endopeptidases, Cysteine Proteinase Inhibitors, Cytoskeletal Proteins, Female, Leupeptins, Mice, Mice, Inbred ICR, Molecular Sequence Data, Multienzyme Complexes, Nerve Tissue Proteins, Neurites, PC12 Cells, Phosphorylation, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Rats, Spodoptera, Wiskott-Aldrich Syndrome Protein, Neuronal, cdc42 GTP-Binding Protein, src-Family Kinases
Dev. Cell
Date: Nov. 01, 2002
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