Anaplastic Lymphoma Kinase Is a Dependence Receptor Whose Proapoptotic Functions Are Activated by Caspase Cleavage

Mourali, Jaouhar; Bénard, Alan; Lourenço, Filipe C.; Monnet, Céline; Greenland, Catherine; Moog-Lutz, Christel; Racaud‐Sultan, Claire; Gonzalez–Dunia, Daniel; Vigny, Marc; Mehlen, Patrick; Delsol, Georges; Allouche, Michèle

doi:10.1128/mcb.01515-05

Cited by 93 publications

(97 citation statements)

References 46 publications

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“…The native full-length ALK receptor is mainly expressed in discrete regions of the developing central and peripheral nervous system (Iwahara et al, 1997). Mourali et al (2006) forced ALK expression in cells of lymphoid and neuronal origin to investigate wild-type ALK functions. They observed that ALK enhanced or triggered apoptosis in these cells and that treatment with agonist antibodies mimicking ALK ligand prevented cell death induction (Mourali et al, 2006).…”

Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

“…Mourali et al (2006) forced ALK expression in cells of lymphoid and neuronal origin to investigate wild-type ALK functions. They observed that ALK enhanced or triggered apoptosis in these cells and that treatment with agonist antibodies mimicking ALK ligand prevented cell death induction (Mourali et al, 2006).…”

Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

“…Receptor cleavage is important for apoptotic function, as mutation of the cleavage site abolishes cell death induction. DCC, neogenin, Ptc, ALK, EphA4 are cleaved once, roughly in the middle of their intracellular domain (Mehlen et al, 1998;Thibert et al, 2003;Matsunaga et al, 2004;Mourali et al, 2006;Furne et al, 2009). The cleavage site of UNC5 receptors is very close to the plasma membrane (Llambi et al, 2001), whereas RET, Trkc and MET have two cleavage sites A new paradigm in cell signaling and cancer therapy D Goldschneider and P Mehlen (Bordeaux et al, 2000;Foveau et al, 2007;TauszigDelamasure et al, 2007).…”

Section: Drs Are Caspase Substratesmentioning

confidence: 99%

“…These receptors are named 'dependence receptors.' To date, the dependence receptor (DR) family is composed of more than a dozen members including DCC (deleted in colorectal carcinoma) (Mehlen et al, 1998), UNC5Hs (uncoordinated 5 homologs), neogenin (Matsunaga et al, 2004), p75 NTR (p75 neurotrophin receptor) (Rabizadeh et al, 1993), RET (rearranged during transfection) (Bordeaux et al, 2000), TrkC (tyrosine kinase receptor C) (Tauszig-Delamasure et al, 2007), Ptc (patched) (Thibert et al, 2003), EphA4 (ephrin type A receptor 4) (Furne et al, 2009), ALK (anaplastic lymphoma kinase) (Mourali et al, 2006), MET (Tulasne et al, 2004) and some integrins (Stupack et al, 2001). All of them are involved in both nervous system development and cancer progression.…”

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confidence: 99%

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Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

Section: Drs Are Caspase Substratesmentioning

confidence: 99%

mentioning

confidence: 99%

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Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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“…ALK is functionally important in embryonic development [3] and in determination of cell survival and cell fate [4]. However, ALK was originally discovered when it was found that the chimeric N-terminal nucleophosmin (NPM) domain/cytoplasmic (catalytic) ALK domain fusion protein (NPM-ALK) is the oncoprotein underlying the pathogenesis of anaplastic large cell lymphomas (ALCL) [5,6].…”

Section: Introductionmentioning

confidence: 99%

Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer

Pérez-Piñera

Chang

Astudillo

et al. 2007

Biochemical and Biophysical Research Communications

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Pleiotrophin (PTN, Ptn) is an 18 kDa cytokine expressed in human breast cancers. Since inappropriate expression of Ptn stimulates progression of breast cancer in transgenic mice and a dominant negative PTN reverses the transformed phenotype of human breast cancer cells that inappropriately express Ptn, it is suggested that constitutive PTN signaling in breast cancer cells that inappropriately express Ptn activates pathways that promote a more aggressive breast cancer phenotype. Pleiotrophin signals by inactivating its receptor, the Receptor Protein Tyrosine Phosphatase (RPTP)β/ζ, and, recently, PTN was found to activate Anaplastic Lymphoma Kinase (ALK) through the PTN/RPTPβ/ζ signaling pathway in PTN-stimulated cells, not through a direct interaction of PTN with ALK and thus not through the PTN-enforced dimerization of ALK. Since full-length ALK is activated in different malignant cancers and activated ALK is a potent oncogenic protein, we examined human breast cancers to test the possibility that ALK may be expressed in breast cancers and potentially activated through the PTN/RPTPβ/ζ signaling pathway; we now demonstrate that ALK is strongly expressed in different histological subtypes of human breast cancer; furthermore, ALK is expressed in both nuclei and cytoplasm and, in the "dotted" pattern characteristic of ALK fusion proteins in anaplastic large cell lymphoma. This study thus supports the possibility that activated ALK may be important in human breast cancers and potentially activated either through the PTN/RPTPβ/ζ signaling pathway, or, alternatively, as an activated fusion protein to stimulate progression of breast cancer in humans.

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Irreversible modifications of receptor tyrosine kinases

2018

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Each group of the 56 receptor tyrosine kinases (RTK) binds with one or more soluble growth factors and coordinates a vast array of cellular functions. These outcomes are tightly regulated by inducible post-translational events, such as tyrosine phosphorylation, ubiquitination, ectodomain shedding, and regulated intramembrane proteolysis. Because of the delicate balance required for appropriate RTK function, cells may become pathogenic upon dysregulation of RTKs themselves or their post-translational covalent modifications. For example, reduced ectodomain shedding and decreased ubiquitination of the cytoplasmic region, both of which enhance growth factor signals, characterize malignant cells. Whereas receptor phosphorylation and ubiquitination are reversible, proteolytic cleavage events are irreversible, and either modification might alter the subcellular localization of RTKs. Herein, we focus on ectodomain shedding by metalloproteinases (including ADAM family proteases), cleavage within the membrane or cytoplasmic regions of RTKs (by gamma-secretases and caspases, respectively), and complete receptor proteolysis in lysosomes and proteasomes. Roles of irreversible modifications in RTK signaling, pathogenesis, and pharmacology are highlighted.

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Anaplastic Lymphoma Kinase Is a Dependence Receptor Whose Proapoptotic Functions Are Activated by Caspase Cleavage

Cited by 93 publications

References 46 publications

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer

Irreversible modifications of receptor tyrosine kinases

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