VEGF upregulates Homer 1a gene expression via the mitogen-activated protein kinase cascade in cultured cortex neurons.

In alternative splice variants of Homer 1 transcripts, Homer 1a messenger RNA (mRNA) has been shown to be upregulated selectively and rapidly by neural stimulation and represents a member of the immediate early gene (IEG) family. In our study, Homer 1 variants were expressed in cultured neurons as investigated by RT-PCR and Western blot analysis. After stimulation of VEGF, neurons selectively upregulated Homer 1a mRNA via Flk-1. The induction of Homer 1a mRNA peaked at 2h and sustained to 8h, while no significant change was observed of Homer 1b/c mRNA levels. Inhibitor analysis as well as Western blot analysis has indicated that the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade plays an important role in VEGF-stimulated induction of Homer 1a mRNA. These results demonstrate that MAPK is a key mediator that links distinct extracellular VEGF stimuli to the transcriptional activation of Homer 1a mRNA.