%0 Journal Article %1 fischerDifferentialTyrosinePhosphorylation2015 %A Fischer, Adrian %A Brummer, Tilman %A Warscheid, Bettina %A Radziwill, Gerald %C Netherlands %D 2015 %J Biochimica et biophysica acta %K 14/*biosynthesis/genetics,Mutation,Phosphorylation/physiology,Platelet-derived Cell Cells,HeLa Cells,Humans,Intracellular Enzymologic/*physiology,Gene Expression Genetic/*physiology,Protein Kinases/genetics/*metabolism,to_read,Tyrosine Knockdown Membrane/enzymology/genetics,CNK1,Gene Metalloproteinase Peptides Proteins/genetics/*metabolism,Matrix Regions Regulation Signaling Techniques,HEK293 Transport/physiology,Scaffold and factor,Promoter growth phosphorylation,Tyrosine/genetics/metabolism protein,Signal transduction,SRC,src-Family %N 11 Pt A %P 2847--2855 %R 10.1016/j.bbamcr.2015.08.014 %T Differential Tyrosine Phosphorylation Controls the Function of CNK1 as a Molecular Switch in Signal Transduction. %V 1853 %X Scaffold proteins are multidomain proteins without enzymatic function that play a central role in coordinating signaling processes. The scaffold protein CNK1 interacts with pathway-specific signaling proteins and thereby regulates these respective pathways. Here, we revealed tyrosine phosphorylation as a critical regulation mechanism to control the function of CNK1. We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression. Contrary, mutants preventing tyrosine phosphorylation promote matrix metalloproteinase MMP14 promoter activity. CNK1-driven cell proliferation partially depends on its tyrosine phosphorylation. Upon PDGF stimulation, CNK1 is recruited to the plasma membrane mediated by SRC. Knock down of CNK1 prevents PDGF-induced SRE-dependent gene expression, MMP14 promoter activity and cell proliferation. Thus, tyrosine phosphorylation is an important mechanism to control the subcellular localization of CNK1 and its distinct biological functions.

@article{fischerDifferentialTyrosinePhosphorylation2015, abstract = {Scaffold proteins are multidomain proteins without enzymatic function that play a central role in coordinating signaling processes. The scaffold protein CNK1 interacts with pathway-specific signaling proteins and thereby regulates these respective pathways. Here, we revealed tyrosine phosphorylation as a critical regulation mechanism to control the function of CNK1. We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression. Contrary, mutants preventing tyrosine phosphorylation promote matrix metalloproteinase MMP14 promoter activity. CNK1-driven cell proliferation partially depends on its tyrosine phosphorylation. Upon PDGF stimulation, CNK1 is recruited to the plasma membrane mediated by SRC. Knock down of CNK1 prevents PDGF-induced SRE-dependent gene expression, MMP14 promoter activity and cell proliferation. Thus, tyrosine phosphorylation is an important mechanism to control the subcellular localization of CNK1 and its distinct biological functions.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {Netherlands}, author = {Fischer, Adrian and Brummer, Tilman and Warscheid, Bettina and Radziwill, Gerald}, biburl = {https://www.bibsonomy.org/bibtex/29c6b020e1558f4c3e8dc7765ec99bd39/warscheidlab}, copyright = {Copyright {\copyright} 2015 Elsevier B.V. All rights reserved.}, doi = {10.1016/j.bbamcr.2015.08.014}, interhash = {aabbe535ac27f05985738cd94c7a2954}, intrahash = {9c6b020e1558f4c3e8dc7765ec99bd39}, issn = {0006-3002}, journal = {Biochimica et biophysica acta}, keywords = {14/*biosynthesis/genetics,Mutation,Phosphorylation/physiology,Platelet-derived Cell Cells,HeLa Cells,Humans,Intracellular Enzymologic/*physiology,Gene Expression Genetic/*physiology,Protein Kinases/genetics/*metabolism,to_read,Tyrosine Knockdown Membrane/enzymology/genetics,CNK1,Gene Metalloproteinase Peptides Proteins/genetics/*metabolism,Matrix Regions Regulation Signaling Techniques,HEK293 Transport/physiology,Scaffold and factor,Promoter growth phosphorylation,Tyrosine/genetics/metabolism protein,Signal transduction,SRC,src-Family}, langid = {english}, month = nov, number = {11 Pt A}, pages = {2847--2855}, pmid = {26319181}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Differential Tyrosine Phosphorylation Controls the Function of {{CNK1}} as a Molecular Switch in Signal Transduction.}, volume = 1853, year = 2015 }