ARTICLE

Cell Research, 15(7):495-503, July 2005

Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

Ana GARCÍA-SACRISTÁN^¶, María J. FERNÁNDEZ-NESTOSA, Pablo HERNÁNDEZ, Jorge B. SCHVARTZMAN, Dora B. KRIMER^*

Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, Madrid 28040, Spain

Received, Mar 24, 2005 Revised, June 7, 2005 Accepted, June 28, 2005

Correspondence: Dora B. KRIMER +34-918-373-112×4238; (phone) dbkrimer@cib.csic.es ¶Present address: Institute of Molecular Medicine, 1649-028, Lisbon Medical School, Lisbon Portugal

Table of Contents Download as printable (PDF) file -858K Full Text (html)file Search Medline for articles by: Dora B. KRIMER

Clk/STY is a LAMMER protein kinase capable to phosphorylate serine/arginine-rich (SR) proteins that modulate pre-mRNA splicing. Clk/STY alternative splicing generates transcripts encoding a full-length kinase and a truncated catalytically inactive protein. Here we showed that clk/STY, as well as other members of the family (e.g. clk2, clk3 and clk4), are up-regulated during HMBA-induced erythroleukemia cell differentiation. mRNAs coding for the full-length and the truncated forms were responsible for the overall increased expression. In clk/STY, however, a switch was observed for the ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more abundant whereas the transcript encoding for the truncated form predominated at latter stages of differentiation. Surprisingly, overexpression of clk/STY did not alter the splicing switch upon differentiation in MEL cells. These results suggest that clk/STY might contribute to control erythroid differentiation by a mechanism that implicates a balance between these two isoforms.

Keywords: clk/STY, LAMMER kinase, alternative splicing, erythroleukemia cells.