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We have developed a proteomic approach for identifying phosphopeptide binding domains that modulate kinase-dependent signaling pathways. An immobilized library of partially degenerate phosphopeptides biased toward a particular protein kinase phosphorylation motif is used to isolate phospho-binding domains that bind to proteins phosphorylated by that kinase.(More)
Polo-like kinases (Plks) perform crucial functions in cell-cycle progression and multiple stages of mitosis. Plks are characterized by a C-terminal noncatalytic region containing two tandem Polo boxes, termed the Polo-box domain (PBD), which has recently been implicated in phosphodependent substrate targeting. We show that the PBDs of human, Xenopus, and(More)
Cullin-RING ligases (CRLs) represent the largest E3 ubiquitin ligase family in eukaryotes, and the identification of their substrates is critical to understanding regulation of the proteome. Using genetic and pharmacologic Cullin inactivation coupled with genetic (GPS) and proteomic (QUAINT) assays, we have identified hundreds of proteins whose stabilities(More)
In eukaryotic cells, the SH2 and PTB domains mediate protein-protein interactions by recognizing phosphotyrosine residues on target proteins. Here we make the unexpected finding that the C2 domain of PKCdelta directly binds to phosphotyrosine peptides in a sequence-specific manner. We provide evidence that this domain mediates PKCdelta interaction with a(More)
Meningiomas are the second most common primary tumor of the brain. Gross-total resection remains the preferred treatment if achievable with minimal morbidity. For incompletely resected or inoperable benign meningiomas, 3D conformal external-beam radiation therapy can provide durable local tumor control in 90 to 95% of cases. Stereotactic radiosurgery (SRS)(More)
In response to certain cytokines and inflammatory mediators, the activity of the neutrophil NADPH oxidase enzyme is primed for enhanced superoxide production when the cells receive a subsequent oxidase-activating stimulus. The relative role of p38 MAPK in the priming and activation processes is incompletely understood. We have developed a 2-step assay that(More)
(PKCδ,-⑀,-θ, and-η) contains a tandem repeated C1 domain and a C2 domain that does not bind calcium. Very recently it was shown that the C2 domain of PKCδ Summary does not bind to phospholipids (Stahelin et al., 2004). PKCδ is known to bind to several proteins, including In eukaryotic cells, the SH2 and PTB domains mediate actin, GAP-43, and possibly SRBC,(More)
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