Differential expression of protein XXXX kinase genes during microglial activation.

@entity16 @entity12186 @entity13720 @entity70547 @entity35 @entity2305 @entity669
Protein @entity669 kinase (PTK) activity is abundant in microglia, but the PTKs that participate in their activation have not been identified. For these studies, we used three paradigms to characterize PTK expression during microglial activation: resting and activated microglia were bulk fractionated from the adult brain, cultured newborn microglia were treated with lipopolysaccharide (LPS) to model the transition from activated toward phagocytic microglia, and PTK expression was examined in activated microglia in situ after facial nerve axotomy. Two PCR-based strategies were used to show that 21 different PTK genes are expressed by @entity35 brain microglia: 5 receptor PTKs, 10 nonreceptor PTKs, and 6 members of the src family. Seven of the 21 PTKs were examined in greater detail. Five PTK mRNAs (fgr, @entity70547 , @entity2305 , @entity13720 , and @entity12186 ) increased expression across all three models of activation. We conclude that they represent key components in the cascades that participate in microglial activation. In contrast, expression of fes and fms correlated with stimuli that affect microglial proliferation. Four of the PTKs ( @entity70547 , fgr, fes, and fms) are believed to be myeloid cell specific and were not expressed by cultured astrocytes. @entity70547 and @entity2305 protein were also not expressed in lysates of immature astrocytes and oligodendrocytes. Because of their putative specificity, these kinases represent potential targets for inhibitors of microglial activation. Because reactive microglia can exacerbate the severity of @entity16 , the identification of specific kinases that participate in microglial activation represents an important advance toward the development of new therapeutics.
