Rap Guanine Nucleotide Exchange Factor 4 (RAPGEF4)

Sequence analysis predicted that the 1,011-amino acid cAMP-GEFII protein contains an N-terminal cAMP-binding domain and a C-terminal GEF domain. Expression of cAMP-GEFI and cAMP-GEFII activated RAP1A after forskolin and 3-isobutyl-1-methylxanthine stimulation, independent of the protein kinase A pathway.

cAMP-GEFI and cAMP-GEFII expression did not activate or only slightly activated other RAS superfamily members after stimulation. Northern blot analysis detected expression of a 4.4-kb cAMP-GEFII transcript that was most prominent in brain and adrenal gland. Within the brain, expression was strongest in cortex, occipital pole, frontal lobe, temporal lobe, amygdala, putamen, hippocampus, and cerebellum.