βPix-b L, a novel isoform of βPix, is generated by alternative translation

Abstract

βPix (Pak-interacting exchange factor) isoforms are recently identified guanine nucleotide exchange factors (GEFs) for Rho family GTPases, Rac/Cdc42, that are key players in the regulation of actin dynamics. Here we show that a novel 105-kDa βPix isoform, βPix-b L, is generated by alternative translation of βPix-b mRNA. Translation of βPix-b L starts at an atypical initiation site, GTG, that is located 57 nucleotides downstream from the newly identified 5 ′ end of βPix-b cDNA. The expression of two isoforms, βPix-b and βPix-b L, from βPix-b mRNA is controlled by an internal ribosome entry site (IRES)-driven mechanism. Comparing to βPix-b, βPix-b L contains additional 105 amino acids composed of a calponin homology (CH) domain and a serine-rich sequence in the N-terminus. The expression of βPix-b L in rat brain is developmentally regulated and high in the embryonic stages, suggesting that the function of βPix-b L is more heavily required during the early stages of brain development.