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: Ana García-Sacristán, María J Fernández-Nestosa, Pablo Hernández, Jorge B Schvartzman, Dora B Krimer
• Journal: Cell research (Cell Res) Vol. 15 Issue 7 Pg. 495-503 (Jul 2005) ISSN: 1001-0602 [Print] England
• PMID: 16045812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Isoenzymes
• Clk dual-specificity kinases
• Protein-Tyrosine Kinases
• Protein Serine-Threonine Kinases
• hexamethylene bisacetamide

Topics

• Acetamides (pharmacology)
• Alternative Splicing (drug effects)
• Animals
• Cell Differentiation (drug effects, physiology)
• Cell Line, Tumor
• Exons
• Gene Expression Regulation, Enzymologic (drug effects)
• Isoenzymes (drug effects, genetics, metabolism)
• Leukemia, Erythroblastic, Acute (drug therapy, enzymology, genetics)
• Mice
• Multigene Family
• Protein Serine-Threonine Kinases (drug effects, genetics, metabolism)
• Protein-Tyrosine Kinases (drug effects, genetics, metabolism)