Kees Jalink
Netherlands Cancer Institute
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Featured researches published by Kees Jalink.
Cell | 1989
Emile van Corven; Alida Groenink; Kees Jalink; Thomas Eichholtz; Wouter H. Moolenaar
Lysophosphatidate (LPA), the simplest natural phospholipid, is highly mitogenic for quiescent fibroblasts. LPA-induced cell proliferation is not dependent on other mitogens and is blocked by pertussis toxin. LPA initiates at least three separate signaling cascades: activation of a pertussis toxin-insensitive G protein mediating phosphoinositide hydrolysis with subsequent Ca2+ mobilization and stimulation of protein kinase C; release of arachidonic acid in a GTP-dependent manner, but independent of prior phosphoinositide hydrolysis; and activation of a pertussis toxin-sensitive Gi protein mediating inhibition of adenylate cyclase. The peptide bradykinin mimics LPA in inducing the first two responses but fails to activate Gi and to stimulate DNA synthesis. Our data suggest that the mitogenic action of LPA occurs through Gi or a related pertussis toxin substrate and that the phosphoinositide hydrolysis-protein kinase C pathway is neither required nor sufficient, by itself, for mitogenesis. The results further suggest that LPA or LPA-like phospholipids may have a novel role in G protein-mediated signal transduction.
EMBO Reports | 2004
Bas Ponsioen; Jun Zhao; Jurgen Riedl; Fried Zwartkruis; Gerard van der Krogt; Manuela Zaccolo; Wouter H. Moolenaar; Johannes L Bos; Kees Jalink
Epac1 is a guanine nucleotide exchange factor for Rap1 that is activated by direct binding of cAMP. In vitro studies suggest that cAMP relieves the interaction between the regulatory and catalytic domains of Epac. Here, we monitor Epac1 activation in vivo by using a CFP–Epac–YFP fusion construct. When expressed in mammalian cells, CFP–Epac–YFP shows significant fluorescence resonance energy transfer (FRET). FRET rapidly decreases in response to the cAMP‐raising agents, whereas it fully recovers after addition of cAMP‐lowering agonists. Thus, by undergoing a cAMP‐induced conformational change, CFP–Epac–YFP serves as a highly sensitive cAMP indicator in vivo. When compared with a protein kinase A (PKA)‐based sensor, Epac‐based cAMP probes show an extended dynamic range and a better signal‐to‐noise ratio; furthermore, as a single polypeptide, CFP–Epac–YFP does not suffer from the technical problems encountered with multisubunit PKA‐based sensors. These properties make Epac‐based FRET probes the preferred indicators for monitoring cAMP levels in vivo.
The EMBO Journal | 1996
F R Postma; Kees Jalink; T Hengeveld; Wouter H. Moolenaar
Sphingosine‐1‐phosphate (S1P) is a bioactive lysosphingolipid implicated in mitogenesis and cytoskeletal remodelling, but its mechanism of action is poorly understood. We report here that in N1E‐115 neuronal cells, S1P mimics the G protein‐coupled receptor agonist lysophosphatidic acid (LPA) in rapidly inducing neurite retraction and soma rounding, a process driven by Rho‐dependent contraction of the actin cytoskeleton. S1P is approximately 100‐fold more potent than LPA in evoking these shape changes, with an EC50 as low as 1.5 nM. Microinjection of S1P has no effect, neither has addition of sphingosine or ceramide. As with LPA, S1P action is inhibited by suramin and subject to homologous desensitization; however, the responses to S1P and LPA do not show cross‐desensitization. We conclude that S1P activates its own high affinity receptor to trigger Rho‐regutated cytoskeletal events. Thus, S1P and LPA may belong to an emerging family of bioactive lysophospholipids that act through distinct G protein‐coupled receptors to mediate similar actions.
Immunity | 2003
Eric Reits; Alexander Griekspoor; Joost Neijssen; Tom A. Groothuis; Kees Jalink; Peter A. van Veelen; Hans Janssen; Jero Calafat; Jan W. Drijfhout; Jacques Neefjes
Antigenic peptides generated by the proteasome have to survive a peptidase-containing environment for presentation by MHC class I molecules. We have visualized the fate and dynamics of intracellular peptides in living cells. We show that peptides are distributed over two different but interconnected compartments, the cytoplasm and the nucleus, and diffuse rapidly through and between these compartments. Since TAP is excluded from the nuclear face of the nuclear envelope, nuclear peptides have to leave the nucleus to contact TAP. Thereby, these peptides encounter cytosolic peptidases that degrade peptides within seconds unless bound to chromatin. Since peptide degradation is far more efficient than translocation, many peptides will be lost for antigen presentation by MHC class I molecules.
The EMBO Journal | 2006
Kristopher Clark; Michiel Langeslag; Bart van Leeuwen; Leonie Ran; Alexey G. Ryazanov; Carl G. Figdor; Wouter H. Moolenaar; Kees Jalink; Frank N. van Leeuwen
Actomyosin contractility regulates various cell biological processes including cytokinesis, adhesion and migration. While in lower eukaryotes, α‐kinases control actomyosin relaxation, a similar role for mammalian α‐kinases has yet to be established. Here, we examined whether TRPM7, a cation channel fused to an α‐kinase, can affect actomyosin function. We demonstrate that activation of TRPM7 by bradykinin leads to a Ca2+‐ and kinase‐dependent interaction with the actomyosin cytoskeleton. Moreover, TRPM7 phosphorylates the myosin IIA heavy chain. Accordingly, low overexpression of TRPM7 increases intracellular Ca2+ levels accompanied by cell spreading, adhesion and the formation of focal adhesions. Activation of TRPM7 induces the transformation of these focal adhesions into podosomes by a kinase‐dependent mechanism, an effect that can be mimicked by pharmacological inhibition of myosin II. Collectively, our results demonstrate that regulation of cell adhesion by TRPM7 is the combined effect of kinase‐dependent and ‐independent pathways on actomyosin contractility.
Biophysical Journal | 2004
Jacco van Rheenen; Michiel Langeslag; Kees Jalink
Imaging of fluorescence resonance energy transfer (FRET) between suitable fluorophores is increasingly being used to study cellular processes with high spatiotemporal resolution. The genetically encoded Cyan (CFP) and Yellow (YFP) variants of Green Fluorescent Protein have become the most popular donor and acceptor pair in cell biology. FRET between these fluorophores can be imaged by detecting sensitized emission. This technique, for which CFP is excited and transfer is detected as emission of YFP, is sensitive, fast, and straightforward, provided that proper corrections are made. In this study, the detection of sensitized emission between CFP and YFP by confocal microscopy is optimized. It is shown that this FRET pair is best excited at 430 nm. We identify major sources of error and variability in confocal FRET acquisition including chromatic aberrations and instability of the excitation sources. We demonstrate that a novel correction algorithm that employs online corrective measurements yields reliable estimates of FRET efficiency, and it is also shown how the effect of other error sources can be minimized.
Nature Methods | 2010
Joachim Goedhart; Laura van Weeren; Mark A. Hink; Norbert O. E. Vischer; Kees Jalink; Theodorus W. J. Gadella
Optimization of autofluorescent proteins by intensity-based screening of bacteria does not necessarily identify the brightest variant for eukaryotes. We report a strategy to screen excited state lifetimes, which identified cyan fluorescent proteins with long fluorescence lifetimes (>3.7 ns) and high quantum yields (>0.8). One variant, mTurquoise, was 1.5-fold brighter than mCerulean in mammalian cells and decayed mono-exponentially, making it an excellent fluorescence resonance energy transfer (FRET) donor.
Journal of Biological Chemistry | 2003
Leo Price; Michiel Langeslag; Jean Paul ten Klooster; Peter L. Hordijk; Kees Jalink; John G. Collard
Rac is activated in response to various stimuli including growth factors and by adhesion to the extracellular matrix. However, how these stimuli ultimately result in Rac activation is poorly understood. The increase in intracellular calcium [Ca2+]i represents a ubiquitous second messenger system in cells, linking receptor activation to downstream signaling pathways. Here we show that elevation of [Ca2+]i, either artificially or by thrombin receptor activation, potently induces Rac activation. Lamellipodia formation induced by artificial elevation of [Ca2+]i is blocked by inhibition of Rac signaling, indicating that calcium-induced cytoskeletal changes are controlled by the activation of Rac. Calcium-dependent Rac activation was dependent on the activation of a conventional protein kinase C. Furthermore, both increased [Ca2+]i and protein kinase C activation induce phosphorylation of RhoGDIα and induce the translocation of cytosolic Rac to the plasma membrane. Intracellular calcium signaling may thus contribute to the intracellular localization and activation of Rac to regulate the cytoskeletal changes in response to receptor stimulation.
Nature | 2015
Guotai Xu; J. Ross Chapman; Inger Brandsma; Jingsong Yuan; Martin Mistrik; Peter Bouwman; Jirina Bartkova; Ewa Gogola; Daniël O. Warmerdam; Marco Barazas; Janneke E. Jaspers; Kenji Watanabe; Mark Pieterse; Ariena Kersbergen; Wendy Sol; Patrick H. N. Celie; Philip C. Schouten; Bram van den Broek; Ahmed M. Salman; Marja Nieuwland; Iris de Rink; Jorma J. de Ronde; Kees Jalink; Simon J. Boulton; Junjie Chen; Dik C. van Gent; Jiri Bartek; Jos Jonkers; Piet Borst; Sven Rottenberg
Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases. In particular, little is known about BRCA1-independent restoration of HR. Here we show that loss of REV7 (also known as MAD2L2) in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX–MDC1–RNF8–RNF168–53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining during immunoglobulin class switch recombination. Our results reveal an unexpected crucial function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells.
The EMBO Journal | 1992
R L van der Bend; J Brunner; Kees Jalink; E J van Corven; Wouter H. Moolenaar; W J van Blitterswijk
Lysophosphatidic acid (LPA) is a naturally occurring phospholipid with hormone‐ and growth factor‐like activities. Exogenous LPA stimulates GTP‐dependent phosphoinositide hydrolysis and inhibits adenylate cyclase in its target cells, but the site of action of LPA is unknown. We now report the identification by photoaffinity labeling of a putative LPA membrane receptor in various LPA‐responsive cell types. A 32P‐labeled LPA analogue containing a photoreactive fatty acid, [32P]diazirine‐LPA, labels a membrane protein of apparent molecular mass of 38–40 kDa in various cell types, including neuronal cells, brain homogenates, carcinoma cells, leukemic cells and normal fibroblasts. Labeling of the 38–40 kDa protein is competitively inhibited by unlabeled 1‐oleoyl‐LPA (IC50 approximately 10 nM), but not by other phospholipids. Specific labeling is not detected in rat liver membranes or in human neutrophils, which are physiologically unresponsive to LPA. Suramin, an inhibitor of both early and late events in the action of LPA, completely inhibits the binding of photoreactive LPA. We suggest that the 38–40 kDa protein represents a specific LPA cell surface receptor mediating at least part of the multiple cellular responses to LPA.