Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.

Original publication

DOI

10.1080/15548627.2015.1034406

Type

Journal article

Journal

Autophagy

Publication Date

01/2015

Volume

11

Pages

1114 - 1129

Addresses

a Inserm U1065 / C3M, Team 2; Cell Death Differentiation Inflammation and Cancer Nice , France.

Keywords

Monocytes, Cell Line, Tumor, Animals, Mice, Inbred C57BL, Humans, Leukemia, Myeloid, Macrophage Colony-Stimulating Factor, Receptors, Purinergic P2, Uridine Diphosphate, Signal Transduction, Cell Differentiation, Enzyme Activation, Models, Biological, Autophagy, Phospholipase C gamma, Calcium-Calmodulin-Dependent Protein Kinase Kinase, AMP-Activated Protein Kinases