Heterogeneous nuclear ribonucleoprotein Q is a novel substrate of SH2 domain-containing phosphatase-2.
SH2 domain-containing phosphatase-2 (SHP2) is a protein-tyrosine phosphatase implicated in activation of cell signalling such as the Ras/extracellular signal-regulated kinase pathway. The substrates of SHP2 and their roles in cell activation are not fully understood. By using the substrate-trapping method with the phosphatase-dead SHP2 mutant, in which C459 was substituted by serine, and the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometric analysis, we found that heterogeneous nuclear ribonucleoprotein Q (hnRNP Q), a protein implicated in RNA metabolisms, was a novel substrate of SHP2. Tyrosine-phosphorylated hnRNP Q was detected in HL-60, Jurkat and human peripheral blood mononuclear cells, but not mature neutrophils, treated with pervanadate. Tyrosine-phosphorylated hnRNP Q was directly bound to SHP2 in vivo and in vitro, and dephosphorylated by SHP2 in vitro. These findings suggest that hnRNP Q is a novel substrate of SHP2 and the SHP2 activity may be also involved in RNA metabolisms via dephosphorylation of hnRNP Q.
Graduate School of Medicine, Department of Physiology, Osaka City University, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Norifumi
N
Watanabe
Takayuki
T
Kato
Hisakazu
H
Fujita
Seiichi
S
Kitagawa
D057809:HEK293 Cells; D018922:HL-60 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000737:chemistry* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
D034441:Heterogeneous-Nuclear Ribonucleoproteins; C425312:SYNCRIP protein, human; D012313:RNA; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
SH2 domain-containing phosphatase-2; heterogeneous nuclear ribonucleoprotein Q; pervanadate