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Strain‐Induced Ets‐2 Phosphorylation by CaMK II in Cranial Suture Development
Author(s) -
Chen JungRen,
Yu Jack C.,
Lin ChaoHsiung,
Wenger Karl H.,
Huang ShunTe,
Borke James L.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.301
Subject(s) - phosphorylation , craniosynostosis , camk , serine , microbiology and biotechnology , intracellular , mechanotransduction , chemistry , biology , anatomy , protein kinase a , autophosphorylation
Understanding the mechanisms of suture mediated regulation of calvarial growth by the antagonistic coupling of these mechanisms holds the promise of a more rational and selective surgical approach to the treatment of children with craniosynostosis. We attempted to construct the early intracellular events resulting from cellular strains within the cranial suture. The objectives were to establish a chain of cause and effect, linking cellular strain to substrate phosphorylation and to identify both the agent and the target sites of phosphorylation. There was rapid increase of intracellular Ca++ in response to tensile stress. We found Serine 246, 310, and 313 were the phosphorylated by CaMK II and the context in which this serine residue was presented was extremely important. MALDI‐TOF mass spectroscopy of the selected nanopeptides treated by CaMK II showed 80 Da shifts consistent with phosphorylation. In conclusion, one of the means for cranial suture cells to respond to tensile forces is by increase in intracellular calcium which causes CaMK II to phosphorylate Ets‐2 and alter Ets‐2 binding to its downstream promoters. Thus, Ets‐2 may be at the intersection of three key signaling pathways, including FGF‐2, TGF‐beta, and mechanotransduction, important in the pathogenesis of craniosynostosis. (NSC 95‐2314‐B‐214‐007‐MY2).