Tyrosine phosphorylation of RNA polymerase II carboxyl-terminal domain by the Abl-related gene product.
The largest subunit of RNA polymerase II contains a C-terminal repeated domain (CTD) that is the site of phosphorylation by serine (threonine) and tyrosine kinases. Phosphorylation of the CTD is correlated with transcription elongation. A number of different kinases have previously been shown to phosphorylate the CTD; among them is a nuclear tyrosine kinase encoded by the c-abl proto-oncogene. The processive and high stoichiometric phosphorylation of RNA polymerase II by c-Abl requires the tyrosine kinase, the SH2 domain, and a CTD-interacting domain (CTD-ID) in the Abl protein. The physiological tyrosine phosphorylation of RNA polymerase II by c-Abl in DNA damage response has previously been demonstrated. Basal tyrosine phosphorylation of RNA polymerase II, however, is observed in cells derived from abl-deficient mice, indicating the existence of other CTD tyrosine kinases. In this report, we show that the tyrosine kinase encoded by an Abl-related gene (Arg) also phosphorylates the CTD in vitro and in transfected cells. The SH2 and kinase domain of Arg are 95% identical to that of c-Abl. However, these two proteins share only 29% identity in the large C-terminal region. Interestingly, a CTD-ID is also found in the C-terminal region of Arg. Mapping studies and sequence analysis have led to the identification of the CTD-ID that is highly conserved among the divergent C-terminal regions of Abl and Arg. These results indicate that tyrosine phosphorylation of RNA polymerase II CTD could be catalyzed by either c-Abl or Arg kinase.
Baskaran
R
R
Department of Biology and Center for Molecular Genetics, University of California at San Diego, La Jolla, California, 92093-0322, USA.
Chiang
G G
GG
Mysliwiec
T
T
Kruh
G D
GD
Wang
J Y
JY
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D000081247:CSK Tyrosine-Protein Kinase; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases
C000715470:MAS1 protein, human; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D014443:Tyrosine; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases; C000631346:CSK protein, human; D012319:RNA Polymerase II