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Dynamin reduces Pyk2 Y402 phosphorylation and Src binding in Osteoclasts

dr.qinan 添加于 2009-5-24 20:20 | 1093 次阅读 | 0 个评论

作者
Bruzzaniti A, Neff L, Sandoval A, Du L, Horne WC, Baron R
摘要
Signaling via the Pyk2-Src-Cbl complex downstream of integrins contributes to the assembly, organization and dynamics of podosomes, the transient adhesion complexes of highly motile cells such as osteoclasts and dendritic cells. We previously demonstrated that the GTPase dynamin is associated with podosomes, regulates actin flux in podosomes and promotes bone resorption by osteoclasts. We report here that dynamin associates with Pyk2, independent of dynamin's GTPase activity, and reduces Pyk2 Y402 phosphorylation in a GTPase-dependent manner, leading to decreased Src binding to Pyk2. Over-expressing dynamin decreased the M-CSF- and adhesion-induced phosphorylation of Pyk2 in osteoclast-like cells, suggesting that dynamin is likely to regulate Src-Pyk2 binding downstream of integrins and growth factor receptors with important cellular consequences. Furthermore, catalytically active Src promotes dynamin-Pyk2 association, and mutating specific Src-phosphorylated tyrosine residues in dynamin blunts the dynamin-induced decrease in Pyk2 phosphorylation. Thus, since Src binds to Pyk2 through its interaction with phospho-Y402, our results suggest that Src activates a negative feedback loop downstream of integrin engagement and other stimuli by promoting both the binding of dynamin to Pyk2-containing complexes and the dynamin-dependent decrease in Pyk2 Y402 phosphorylation, ultimately leading to the dissociation of Src from Pyk2.
详细资料
- 文献种类: Journal Article
- 期刊名称: Molecular and Cellular Biology
- 期刊缩写: Mol Cell Biol
- 期卷页: 2009年
- 地址: Department of Oral Biology, Indiana University School of Dentistry, Indianapolis, IN 46202; Department of Orthopedics, Yale University School of Medicine, New Haven, CT 06510; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115; and Department of Medicine, Harvard Medical School, Boston, MA 02115
- ISBN: 1098-5549
- 备注:PMID:19380485
学科领域生物医药 » 生物学
标签

Dynamin Src
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