Engagement of beta2 integrins recruits 14-3-3 proteins to c-Cbl in human neutrophils.

We found that engagement of beta2 integrins on human neutrophils triggered both tyrosine and serine phosphorylation of c-Cbl. Pretreatment of the neutrophils with the broad range protein kinase C (PKC) inhibitor GF-109203X blocked the serine but not the tyrosine phosphorylation of c-Cbl. Moreover, the Src kinase inhibitor PP1 prevented the ...
beta2 integrin-induced tyrosine phosphorylation of c-Cbl but not the simultaneous serine phosphorylation. These results indicate that Src family kinases and PKC can separately modulate the properties of c-Cbl. Indeed, tyrosine kinase-dependent phosphorylation of c-Cbl regulated the ubiquitin ligase activity of that protein, whereas PKC-dependent phosphorylation of c-Cbl had no such effect. Instead, c-Cbl that underwent PKC-induced serine phosphorylation associated with the scaffolding and anti-apoptotic 14-3-3 proteins. Consequently, c-Cbl can independently target proteins for degradation or intracellular localization and may initiate an anti-apoptotic signal in neutrophils.
Mesh Terms:
14-3-3 Proteins, Antigens, CD18, Cell Adhesion, Enzyme Inhibitors, Humans, Indoles, Maleimides, Neutrophils, Phosphorylation, Precipitin Tests, Protein Kinase C, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Serine, Signal Transduction, Tyrosine, Tyrosine 3-Monooxygenase, Ubiquitin, Ubiquitin-Protein Ligases, src-Family Kinases
Biochem. Biophys. Res. Commun.
Date: May. 14, 2004
Download Curated Data For This Publication
136384
Switch View:
  • Interactions 1
  • PTM Genes 1