The regulatory subunit of protein kinase CK2 is a specific A-Raf activator.
Two protein kinases that are involved in proliferation and oncogenesis but so far were thought to be functionally independent are Raf and CK2. The Raf signaling pathway is known to play a critical role in such fundamental biological processes as cellular proliferation and differentiation. Abnormal activation of this pathway is potentially oncogenic. Protein kinase CK2 exhibits enhanced levels in solid human tumors and proliferating tissue. In a two-hybrid screen of a mouse-embryo cDNA library we detected an interaction between A-Raf and CK2beta subunit. This binding was specific, as no interaction between CK2beta and B-Raf or c-Raf-1 was observed. Regions critical for this interaction were localized between residues 550 and 569 in the A-Raf kinase domain. A-Raf kinase activity was enhanced 10-fold upon coexpression with CK2beta in Sf9 cells. The alpha subunit of CK2 abolishes this effect. This is the first demonstration of both a direct Raf-isoform-specific activation and a regulatory role for CK2beta independent of the CK2alpha subunit. The present data thus link two different protein kinases that were thought to work separately in the cell.
Hagemann
C
C
Institut für med. Strahlenkunde und Zellforschung, Bayerische Julius-Maximillians-Universität, Würzburg, Germany.
Kalmes
A
A
Wixler
V
V
Wixler
L
L
Schuster
T
T
Rapp
U R
UR
D000818:Animals; D047390:Casein Kinase II; D002460:Cell Line; D003001:Cloning, Molecular; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D018411:Spodoptera; D013379:Substrate Specificity
D011518:Proto-Oncogene Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf