CacyBP/SIP binds ERK1/2 and affects transcriptional activity of Elk-1.
In this work we showed for the first time that mouse CacyBP/SIP interacts with extracellular signal regulated kinases 1 and 2 (ERK1/2). We also established that a calcium binding protein, S100A6, competes for this interaction. Moreover, the E217K mutant of CacyBP/SIP does not bind significantly to ERK1/2 although it retains the ability to interact with S100A6. Molecular modeling shows that the E217K mutation in the 189-219 CacyBP/SIP fragment markedly changes its electrostatic potential, suggesting that the binding with ERK1/2 might have an electrostatic character. We also demonstrate that CacyBP/SIP-ERK1/2 interaction inhibits phosphorylation of the Elk-1 transcription factor in vitro and in the nuclear fraction of NB2a cells. Altogether, our data suggest that the binding of CacyBP/SIP with ERK1/2 might regulate Elk-1 phosphorylation/transcriptional activity and that S100A6 might further modulate this effect via Ca(2+)-dependent interaction with CacyBP/SIP and competition with ERK1/2.
Kilanczyk
Ewa
E
Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland.
Filipek
Slawomir
S
Jastrzebska
Beata
B
Filipek
Anna
A
D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D047468:Immunoprecipitation; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D010766:Phosphorylation; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism*
C111922:Cacybp protein, mouse; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C494113:Elk1 protein, mouse; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C489134:S100a6 protein, mouse; D050807:ets-Domain Protein Elk-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3