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

作　　者：Ana GARCíA-SACRISTáN■ María J. FERNáNDEZ-NESTOSA Pablo HERNáNDEZ Jorge B.SCHVARTZMAN Dora B. KRIMER 

机构地区：[1]Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de InvestigacionesCientíficas, Ramiro de Maeztu 9, Madrid 28040, Spain Instiute of Molecular Medicine,1649-028,Lisbon Medical School,Lisbon Portugal,Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de InvestigacionesCientíficas, Ramiro de Maeztu 9, Madrid 28040, Spain,Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de InvestigacionesCientíficas, Ramiro de Maeztu 9, Madrid 28040, Spain,Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de InvestigacionesCientíficas, Ramiro de Maeztu 9, Madrid 28040, Spain,Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, Consejo Superior de InvestigacionesCientíficas, Ramiro de Maeztu 9, Madrid 28040, Spain

出　　处：《Cell Research》2005年第7期495-503,共9页细胞研究（英文版）

摘　　要：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 catalyti-cally 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 thetruncated forms were responsible for the overall increased expression. In clk/STY, however, a switch was observed forthe ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more abundantwhereas 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 thatclk/STY might contribute to control erythroid differentiation by a mechanism that implicates a balance between thesetwo isoforms.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 erythroleukernia 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.

关 键 词：蛋白质激酶 clk/STY 红白血病 病理机制 磷酸化 丝氨酸 精氨酸 

分 类 号：R733.7[医药卫生—肿瘤]