Regulation of protein kinases; controlling activity through activation segment conformation.

By B. Nolen, Susan S. Taylor, G. Ghosh. Molecules and Cells, 2004

1,134 citations recorded by the source corpus.

Subfields: Computational Theory and Mathematics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e37aac20ad2167538f70b77249d42d188159a69c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Computational Theory and Mathematics

1. T. Dever
2. Frank Sicheri
3. R. Roskoski
4. A. Dar
5. Z. Du
6. Christine Lovly

In Molecular Biology

1. Matthias Mann
2. Jesper V. Olsen
3. Florian Gnad
4. T. Dever
5. Frank Sicheri
6. R. Roskoski
7. A. Dar
8. Z. Du

Citations in the corpus

• Mechanisms of receptor tyrosine kinase activation in cancer (2018, positive): “FGFR, IR, and IGF-1R receptors are autoinhibited by the activation loop, which directly contacts the active site of the kinase and disrupts ATP and substrate binding [21, 22].”
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. (2008, background): “Regulated Site-Specific Phosphorylation of Kinases with Known and Potential Mitotic Functions Major kinase regulators of cell-cycle progression such as CDC2/ CDK1 and PLK1 are phosphorylated in trans at their activation segments by upstream acting kinases, whereas others such as the Aurora kinases m”
• Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a Pseudomonas syringae effector. (2010, background): “…arginine immediately preceding the invariant aspartate in subdomain VI essential for catalytic activity, and the phosphorylation of the activation loop often is required for the activation of RD kinases (Nolen et al., 2004), we inspected potential phosphorylation sites in the activation loop.”
• The ErbB/HER family of protein-tyrosine kinases and cancer. (2014, background): “Although phosphorylation of one or more esidues in the activation segment of most protein kinases is equired for activation [54] and phosphorylation of EGFR Tyr869 n the activation segment occurs [63], this phosphorylation is ot required for activation [55,56].”
• Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. (2006, background): “Another important conformational change in kinases is the motion of the activation loop from the inactive to the catalytically active form, which in many kinases results in the reorganization of the active site including the aspartate that chelates Mg or other divalent cations (Nolen et al., 2004).”
• Higher-Order Substrate Recognition of eIF2α by the RNA-Dependent Protein Kinase PKR (2005, positive): “The activation segments of PKR in the P3221 crystal form and of one PKR molecule in the P21 crystal form are stoichiometrically phosphorylated on Thr446 and adopt a fully structured winding conformation generally indicative of a catalytically competent state (Johnson et al., 1996; Nolen et al., 2004”
• Kinase-targeted cancer therapies: progress, challenges and future directions (2018, background): “The active or inactive state of the protein kinase is determined by the position of the A-loop, including the DFG motif at its N-terminal, which has various conformations [28, 98, 134, 135].”