Tyrosine phosphorylation controls nuclear localization and transcriptional activity of Ssdp1 in mammalian cells.
The LIM-HD proteins interact with different cofactors, including Ssdp1 to regulate development in a diverse range of species. The single stranded DNA binding protein (Ssdp1) is a member of an evolutionarily conserved family of proteins that regulate critical transcriptional processes during embryonic development. Ssdp1 is localized predominantly in the cytoplasm of 293T cells but is translocated to the nucleus when co-transfected with Lck, a member of the Src family of non-receptor tyrosine kinases. The Src tyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex. We propose that phosphorylation involving N-terminal tyrosine residues of Ssdp1 is a means of regulating its nuclear localization and subsequent transcriptional activation of LIM-HD complexes.
Dey-Guha
Ipsita
I
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, HHS, Bethesda, Maryland 20892, USA.
Malik
Nasir
N
Lesourne
Renaud
R
Love
Paul E
PE
Westphal
Heiner
H
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism*
C412373:AG 1879; D004268:DNA-Binding Proteins; D011743:Pyrimidines; C504094:SSBP3 protein, human; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)