Engagement of beta2 integrins recruits 14-3-3 proteins to c-Cbl in human neutrophils |
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Authors: | Melander Fredrik Andersson Tommy Dib Karim |
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Institution: | Experimental Pathology, Department of Laboratory Medicine, Lund University, Malm? University Hospital, Entrance 78, SE-205 02 Malm?, Sweden. |
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Abstract: | 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. |
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Keywords: | c-Cbl Human neutrophils Protein kinase C Src tyrosine kinase Ubiquitin ligase |
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