Structural Basis for Control by Phosphorylation

Johnson, L.N.; Lewis, Richard J.

doi:10.1021/cr000225s

Cited by 566 publications

(505 citation statements)

References 177 publications

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“…Phosphorylation plays a major role in propagating the transduction of extracellular stimuli in a sensitive, selective and temporally ordered manner [49,55]. This in turn, functions to activate a diverse cascade of signaling pathways which ultimately culminate in the regulation of global cellular processes [49,[55][56][57].…”

Section: Protein Kinasesmentioning

confidence: 99%

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

Baron

et al. 2012

Oncogene

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Section: Protein Kinasesmentioning

confidence: 99%

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

Baron

et al. 2012

Oncogene

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“…Phosphorylation of the activation loop induces it to refold, causing subtle conformational changes which reverberate through the rest of the enzyme [15]. For example, in the ERK2 MAPK, activation loop phosphorylation unblocks the active site and promotes a closure of the upper and lower lobes of the kinase domain that brings the catalytic residues into their correct orientation [16]. As a result, the catalytic rate of ERK2 is increased by over 5000-fold [15].…”

Section: Introductionmentioning

confidence: 99%

Analysis of mitogen-activated protein kinase activation and interactions with regulators and substrates

Bardwell

Shah

2006

Methods

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Mitogen-activated protein kinase (MAPK) cascades are ubiquitous signal transduction modules in eukaryotes that are of great interest and importance. Here, we summarize some useful methods for the analysis of MAPK signaling, including methods to (1) detect MAPK activation in cells, with an emphasis on using phosphorylation-state-specific antibodies raised against mammalian phosphopeptide sequences to detect the activation of MAPKs in other species; (2) estimate the cellular concentrations of MAPKs and other proteins of interest; (3) detect and quantify the stable physical association of MAPKs with their substrates and regulators, and estimate the relevant dissociation constants; (4) delineate the MAPK-binding regions or domains of MAPK-interacting proteins, with particular emphasis on the identification and verification of MAPK-docking sites. These procedures are broadly applicable to many organisms, including both yeast and mammalian cells.

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“…This is especially the case for so‐called ‘RD’ kinases, which contain an arginine in the highly conserved HRD motif in the catalytic loop. The Arg residue in this motif creates a basic pocket together with a Lys residue located C‐terminally of the DFG motif that accommodates the phosphate group of the phospho‐Ser/Thr residue in the activation loop 3. In many cases, phosphorylation of activation segment residue(s) is dependent on the activity of an upstream kinase, but many kinases also possess an inherent autophosphorylation activity, which is physiologically relevant in many cases 4.…”

mentioning

confidence: 99%

Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation

et al. 2018

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The protein kinase D (PKD) family is regulated through multi‐site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser‐742 (and Ser‐738 in vitro) in the activation loop and Ser‐910 in the C‐tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P + 1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance. In cells, PKD Tyr autophosphorylation is suppressed through the association of an inhibitory factor. Our findings provide important novel insights into PKD (auto)regulation.

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Structural Basis for Control by Phosphorylation

Cited by 566 publications

References 177 publications

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

Analysis of mitogen-activated protein kinase activation and interactions with regulators and substrates

Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation

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