9 p. ; 24 cm.Includes bibliographical references

Alberich-Jorda, Meritxell

Battista, Natalia

Delwel, Ruud

Lom, Kirsten

Löwenberg, Bob

Maccarrone, Mauro

Rayman, Nazik

Tas, Marjolein

Verbakel, Sandra

Schwarz, Herbert Ferlando, 1883-1960.

American Museum of Natural History Scientific Publications

Paranthidium, Anthidiellum, and Hypanthidium

Cb2, the gene encoding the peripheral cannabinoid receptor, is located in\n      a common virus integration site and is overex-pressed in retrovirally\n      induced murine myeloid leukemias. Here we show that this G protein-coupled\n      receptor (GPCR) is also aberrantly expressed in a high percentage of human\n      acute myeloid leukemias. We investigated the mechanism of transformation\n      by Cb2 and demonstrate that aberrant expression of this receptor on\n      hematopoietic precursor cells results in distinct effects depending on the\n      ligand used. Cb2-expressing myeloid precursors migrate upon stimulation by\n      the endocannabinoid 2-arachidonoylglycerol and are blocked in neutrophilic\n      differentiation upon exposure to another ligand, CP55940. Both effects\n      depend on the activation of G(alphai) proteins and require the\n      mitogen-induced extracellular kinase/extracellular signal-regulated kinase\n      (MEK/ERK) pathway. Down-regulation of cyclic adenosine monophosphate\n      (cAMP) levels upon G(alphai) activation is important for migration\n      induction but is irrelevant for the maturation arrest. Moreover, the\n      highly conserved G protein-interacting DRY motif, present in the second\n      intracellular loop of GPCRs, is critical for migration but unimportant for\n      the differentiation block. This suggests that the Cb2-mediated\n      differentiation block requires interaction of G(alphai) proteins with\n      other currently unknown motifs. This indicates a unique mechanism by which\n      a transforming GPCR, in a ligand-dependent manner, causes 2 distinct\n      oncogenic effects: altered migration and block of neutrophilic\n      development

Alberich-Jorda, M. (Meritxell)

Rayman, N. (Nazik)

Tas, M. (Marjolein)

Verbakel, S.E. (Sandra)

Battista, N. (Natalia)

Lom, K. (Kirsten) van

L\xc3\xb6wenberg, B. (Bob)

Maccarrone, M. (Mauro)

Delwel, H.R. (Ruud)

Erasmus University Digital Repository

The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner

http://repub.eur.nl/pub/8184/15039279.pdf

Paranthidium, Anthidiellum, and Hypanthidium

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American Museum of Natural History Scientific Publications

Erasmus University Digital Repository