NEURABIN IS A SYNAPTIC PROTEIN LINKING P70 S6 KINASE AND THE NEURONALCYTOSKELETON

p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that pl ays a central role in the control of mRNA translation. It physiologica lly phosphorylates the S6 protein of the 40s ribosomal subunit in resp onse to mitogenic stimuli and is a downstream component of the rapamyc in-sensitive pathway, which includes the 12-kDa FK506 binding protein and includes rapamycin and the 12-kDa FK506 binding protein target 1, Here,,ve report the identification of neurabin (neural tissue-specific F-actin binding protein), a neuronally enriched protein of 1,095 amin o acids that contains a PDZ domain and binds p70(S6k). We demonstrate the neurabin-p70(S6k) interaction by yeast two-hybrid analysis and bio chemical techniques, p70S6k and neurabin coimmunoprecipitate from tran sfected HEK293 cells. Site-directed mutagenesis of neurabin implicates its PDZ domain in the interaction with p70S6k, and deletion of the ca rboxyl-terminal five amino acids of p70(S6k) abrogates the interaction , Cotransfection of neurabin in HEK293 cells activates p70(S6k) kinase activity. The mRNA of neurabin and p70S6k show striking colocalizatio n in brain sections by in situ hybridization, Subcellular fractionatio n of rat brain demonstrates that neurabin and p70(S6k) both localize t o the soluble fraction of synaptosomes. By way of its PDZ domain, the neuronal-specific neurabin may target p70(S6k) to nerve terminals.