KIS IS A PROTEIN-KINASE WITH AN RNA RECOGNITION MOTIF

Protein phosphorylation is involved at multiple steps of RNA processin g and in the regulation of protein expression, We present here the fir st identification of a serine/threonine kinase that possesses an RNP-t ype RNA recognition motif: KIS. We originally isolated KIS in a two-hy brid screen through its interaction with stathmin, a small phosphoprot ein proposed to play a general role in the relay and integration of di verse intracellular signaling pathways. Determination of the primary s equence of KIS shows that it is formed by the juxtaposition of a kinas e core with little homology to known kinases and a C-terminal domain t hat contains a characteristic RNA recognition motif with an intriguing homology to the C-terminal motif of the splicing factor U2AF, KIS pro duced in bacteria has an autophosphorylating activity and phosphorylat es stathmin on serine residues. It also phosphorylates in vitro other classical substrates such as myelin basic protein and synapsin but not histones that inhibit its autophosphorylating activity, Immunofluores cence and biochemical analyses indicate that KIS overexpressed in HEK2 93 fibroblastic cells is partly targetted to the nucleus. Altogether, these results suggest the implication of KIS in the control of traffic king and/or splicing of RNAs probably through phosphorylation of assoc iated factors.