Function of RNH-1/14-3-3 beta gene in cellular differentiation and proliferation

It has recently been reported that the members of 14-3-3 protein family participate in cell cycle control and associate with Raf, Bcr, Bcr-Abl, and polyomavirus middle tumor antigen (MT) as modulators of signal transduction. During cDNA cloning for the 17-kDa neuronal differentiation factor (K2 factor) secreted from rat hepatoma Kagura-2 (K2) cells from a K2 cDNA library using rat prepronerve growth factor (prepro NGF) cDNA as a probe, we obtained RNH-1 (rat NGF homologue) clone, which was identified as 14-3-3 beta cDNA, but not K2 factor, although no significant homology is present between 14-3-3 beta and prepro NGF cDNAs. RNH-1/14-3-3 beta gene was markedly expressed as a 2.9-kb mRNA in K2 cells and in newborn rat brain tissue. In PC12 cells the expression of this gene was down-regulated during the neuronal differentiation primed by NGF. The enforced expression of RNH-1/14-3-3 beta in PC12 and K2 cells conferred on them a higher sensitivity to NGF for neuronal differentiation and an intense growth ability in low serum medium, respectively. These results provide additional evidence that RNH-1/14-3-3 beta protein participates in cellular differentiation, proliferation and transformation through the signal transduction pathways of various growth factors.