title: Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, Madrid 28040, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: María J
authors.initials: MJ
authors.lastname: Fernández-Nestosa
authors.forename: Pablo
authors.initials: P
authors.lastname: Hernández
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Schvartzman
authors.forename: Dora B
authors.initials: DB
authors.lastname: Krimer
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D017398:Alternative Splicing / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D005810:Multigene Family; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D000081:Acetamides; D007527:Isoenzymes; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C014026:hexamethylene bisacetamide