Heterogeneous nuclear ribonucleoprotein Q is a novel substrate of SH2 domain-containing phosphatase-2

• Published in: Journal of biochemistry (Tokyo) 2013-11, Vol.154 (5), p.475-480
• Main Authors: Watanabe, Norifumi, Kato, Takayuki, Fujita, Hisakazu, Kitagawa, Seiichi
• Format: Article
• Language: English
• Subjects: HEK293 Cells; Heterogeneous-Nuclear Ribonucleoproteins - genetics; Heterogeneous-Nuclear Ribonucleoproteins - metabolism; HL-60 Cells; Humans; Jurkat Cells; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - metabolism; Mass Spectrometry; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - chemistry; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism; RNA - metabolism
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvt078

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.