Abstract
Protein phosphorylation is involved at multiple steps of RNA processing and in the regulation of protein expression. We present here the first identification of a serine/threonine kinase that possesses an RNP-type RNA recognition motif: KIS. We originally isolated KIS in a two-hybrid screen through its interaction with stathmin, a small phosphoprotein proposed to play a general role in the relay and integration of diverse intracellular signaling pathways. Determination of the primary sequence of KIS shows that it is formed by the juxtaposition of a kinase core with little homology to known kinases and a C-terminal domain that contains a characteristic RNA recognition motif with an intriguing homology to the C-terminal motif of the splicing factor U2AF. KIS produced in bacteria has an autophosphorylating activity and phosphorylates 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. Immunofluorescence and biochemical analyses indicate that KIS overexpressed in HEK293 fibroblastic cells is partly targetted to the nucleus. Altogether, these results suggest the implication of KIS in the control of trafficking and/or splicing of RNAs probably through phosphorylation of associated factors.
Highlights
Evidence is growing that controls of RNA processing and translation are major mechanisms associated with the regulation of gene expression in eukaryotes
We previously identified a domain of KIS as interacting with stathmin in the two-hybrid system [10]
We demonstrate the expression of the KIS gene, the actual kinase activity of KIS protein, and the presence of a C-terminal RNA recognition motif
Summary
(Received for publication, February 13, 1997, and in revised form, June 20, 1997). Alexandre Maucuer‡, Sylvie Ozon, Valerie Manceau, Olivier Gavet, Sean Lawler, Patrick Curmi, and Andre Sobel. Immunofluorescence and biochemical analyses indicate that KIS overexpressed in HEK293 fibroblastic cells is partly targetted to the nucleus. These results suggest the implication of KIS in the control of trafficking and/or splicing of RNAs probably through phosphorylation of associated factors. Evidence is growing that controls of RNA processing and translation are major mechanisms associated with the regulation of gene expression in eukaryotes. These controls involve numerous RNA-protein interactions mediated by protein domains that in most cases are characterized by specific sequence features One or more RRMs are found in a variety of RNA-binding proteins, and the identification within a sequence of an RRM is a strong indication that the function of this protein involves binding to RNA [2]
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