The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation.
YT521-B is a ubiquitously expressed nuclear protein that changes alternative splice site usage in a concentration dependent manner. YT521-B is located in a dynamic nuclear compartment, the YT body. We show that YT521-B is tyrosine phosphorylated by c-Abl in the nucleus. The protein shuttles between nucleus and cytosol, where it can be phosphorylated by c-Src or p59(fyn). Tyrosine phosphorylation causes dispersion of YT521-B from YT bodies to the nucleoplasm. Whereas YT bodies are soluble in non-denaturing buffers, the phosphorylated, dispersed form is non-soluble. Non-phosphorylated YT521-B changes alternative splice site selection of the IL-4 receptor, CD44 and SRp20, but phosphorylation of c-Abl minimizes this concentration dependent effect. We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.
Rafalska
Ilona
I
University of Erlangen, Institute for Biochemistry, Germany.
Zhang
Zhaiyi
Z
Benderska
Natalya
N
Wolff
Horst
H
Hartmann
Annette M
AM
Brack-Werner
Ruth
R
Stamm
Stefan
S
D017398:Alternative Splicing / Q000502:physiology*; D000081247:CSK Tyrosine-Protein Kinase; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases
D009419:Nerve Tissue Proteins; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D019948:Receptors, Interleukin-4; C490769:YTHDC1 protein, human; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases; C000631346:CSK protein, human