Mutation of potential MAPK phosphorylation sites in the Notch antagonist Hairless

Anja C. Nagel; Anette Preiss

doi:10.1111/hrd2.00066

Identification and Functional Characterization of ERK/MAPK Phosphorylation Sites in the Runx2 Transcription Factor

Journal of Biological Chemistry ◽

10.1074/jbc.m109.040980 ◽

2009 ◽

Vol 284 (47) ◽

pp. 32533-32543 ◽

Cited By ~ 149

Author(s):

Chunxi Ge ◽

Guozhi Xiao ◽

Di Jiang ◽

Qian Yang ◽

Nan E. Hatch ◽

...

Keyword(s):

Transcription Factor ◽

Functional Characterization ◽

Phosphorylation Sites ◽

Mapk Phosphorylation ◽

Erk Mapk

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Identification of MAPK Phosphorylation Sites and Their Role in the Localization and Activity of Hypoxia-inducible Factor-1α

Journal of Biological Chemistry ◽

10.1074/jbc.m605058200 ◽

2006 ◽

Vol 281 (44) ◽

pp. 33095-33106 ◽

Cited By ~ 155

Author(s):

Ilias Mylonis ◽

Georgia Chachami ◽

Martina Samiotaki ◽

George Panayotou ◽

Efrosini Paraskeva ◽

...

Keyword(s):

Hypoxia Inducible Factor ◽

Phosphorylation Sites ◽

Mapk Phosphorylation ◽

Hypoxia Inducible Factor 1Α

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Specificity determinants of phosphoprotein phosphatases controlling kinetochore functions

Essays in Biochemistry ◽

10.1042/ebc20190065 ◽

2020 ◽

Vol 64 (2) ◽

pp. 325-336 ◽

Cited By ~ 1

Author(s):

Dimitriya H. Garvanska ◽

Jakob Nilsson

Keyword(s):

Spindle Assembly Checkpoint ◽

Activity Level ◽

Phosphorylation Sites ◽

Binding Affinities ◽

Mitotic Kinases ◽

Anaphase Onset ◽

Phosphoprotein Phosphatases ◽

Linear Motifs ◽

Temporal And Spatial ◽

Kinetochore Function

Abstract Kinetochores are instrumental for accurate chromosome segregation by binding to microtubules in order to move chromosomes and by delaying anaphase onset through the spindle assembly checkpoint (SAC). Dynamic phosphorylation of kinetochore components is key to control these activities and is tightly regulated by temporal and spatial recruitment of kinases and phosphoprotein phosphatases (PPPs). Here we focus on PP1, PP2A-B56 and PP2A-B55, three PPPs that are important regulators of mitosis. Despite the fact that these PPPs share a very similar active site, they target unique ser/thr phosphorylation sites to control kinetochore function. Specificity is in part achieved by PPPs binding to short linear motifs (SLiMs) that guide their substrate specificity. SLiMs bind to conserved pockets on PPPs and are degenerate in nature, giving rise to a range of binding affinities. These SLiMs control the assembly of numerous substrate specifying complexes and their position and binding strength allow PPPs to target specific phosphorylation sites. In addition, the activity of PPPs is regulated by mitotic kinases and inhibitors, either directly at the activity level or through affecting PPP–SLiM interactions. Here, we discuss recent progress in understanding the regulation of PPP specificity and activity and how this controls kinetochore biology.

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THE DYNACTOME: INVESTIGATING DYNAMIC KINASE NETWORKS IN CELLULAR DECISION-MAKING

Clinical & Investigative Medicine ◽

10.25011/cim.v31i4.4827 ◽

2008 ◽

Vol 31 (4) ◽

pp. 22

Author(s):

Jonathan So ◽

Kelly Elder ◽

Anna Dai ◽

Claus Jorgensen ◽

Rune Linding ◽

...

Keyword(s):

Spectrometric Analysis ◽

Phosphorylation Sites ◽

Complex Samples ◽

Downstream Signaling ◽

Through Flow ◽

Colorectal Cancer Cells ◽

Induced Apoptosis ◽

Cell Phenotypes ◽

Kinase Phosphorylation ◽

Kinase Expression

Networks of kinases play a role in the transmission and integration of signals from the membrane to the nucleus. We aim to elucidate kinase phosphorylation and interaction partners in these networks through the immuno-precipitation and mass spectrometric analysis of a representative set of 100 Flag-tagged kinases stably expressed in human colorectal cancer cells. The goal is to generate a comprehensive set of interactions and dynamic phosphorylation sites which correlate with cell phenotypes such as apoptosis and proliferation. The techniques of mass-spectrometry have allowed for the identification of proteins and their phosphorylation sites in complex samples. Various labeling methods such as iTRAQ has enabled the relative quantification of these sites as afunction of time (White et al. PNAS, 2007). However, kinases usually work in the context of particular signaling stimuli. We aim to characterize the role of these over-expressed kinases in the context of Trail-induced apoptosis. This isparticularly relevant to tumorigenesis in that many cancers are resistant to apoptosis and recombinant Trail therapies are currently undergoing clinical trials. We present assays to correlate the proliferative ability and sensitivity to apoptosis of various stable cell lines with kinase expression levels through flow cytometry. We also present efforts to trace downstream signaling through the monitoring of MAP kinase phosphorylation using a high-throughput bead array.

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