Signaling to the DEAD box--regulation of DEAD-box p68 RNA helicase by protein phosphorylations.
P68 nuclear RNA helicase is essential for normal cell growth. The protein plays a very important role in cell development and proliferation. However, the molecular mechanism by which the p68 functions in cell developmental program is not clear. We previously observed that bacterially expressed his-p68 was phosphorylated at multiple sites including serine/threonine and tyrosine [L. Yang, Z.R. Liu, Protein Expr. Purif., 35: 327]. Here we report that p68 RNA helicase is phosphorylated at tyrosine residue(s) in HeLa cells. Phosphorylation of p68 at threonine or tyrosine residues responds differently to tumor necrosis factor alpha (TNF-alpha)induced cell signal. Kinase inhibition and in vitro kinase assays demonstrate that p68 RNA helicase is a cellular target of p38 MAP kinase. Phosphorylation of p68 affects the ATPase and RNA unwinding activities of the protein. In addition, we demonstrate here that phosphorylation of p68 RNA helicase controls the function of the protein in the pre-mRNA splicing process. Interestingly, phosphorylation at different amino acid residues exhibits different regulatory effects. The data suggest that function(s) of p68 RNA helicase may be subjected to the regulation of multiple cell signal pathways.
Yang
Liuqing
L
Department of Biology, Georgia State University, University Plaza, Atlanta, GA 30303, USA.
Lin
Chunru
C
Liu
Zhi-Ren
ZR
D053487:DEAD-box RNA Helicases; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D020365:RNA Helicases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D007093:Imidazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D013912:Threonine; D014443:Tyrosine; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; C093642:SB 203580