title: A transient dephosphorylation of JAK1 and JAK2 characterises the early-phase response of murine erythroleukemia cells to the differentiation inducer hexamethylenebisacetamide.
abstract: Although dephosphorylation of tyrosine containing proteins is considered a necessary step in the induction of leukemia cell differentiation by hybrid polar compounds (HPC), the crucial actors in this step remain unknown. We present evidence that tyrosine phosphorylation of JAK1 and JAK2 is down-regulated in murine erythroleukemia cells (MELC) within the first 6 h of their exposure to the prototype of the HPC family, hexamethylenebisacetamide (HMBA), with full recovery at 14 h. Further evidence that the JAKs-centered signalling pathway is switched off early by HMBA was provided by the demonstration that STAT5, a downstream member of this pathway, turned out to be completely dephosphorylated at 6 h in HMBA-treated cells. This JAKs dephosphorylation did not occur in HMBA-resistant clones, suggesting that JAKs are possible targets of the dephosphorylative process required for leukemia cell commitment to differentiation. These results may have impact on leukemia therapy based on JAKs inhibitors.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Firenze, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Arcangeli
authors.forename: L
authors.initials: L
authors.lastname: Fontana
authors.forename: O
authors.initials: O
authors.lastname: Crociani
authors.forename: A
authors.initials: A
authors.lastname: Cherubini
authors.forename: G
authors.initials: G
authors.lastname: Hofmann
authors.forename: E
authors.initials: E
authors.lastname: Piccini
authors.forename: S
authors.initials: S
authors.lastname: Polvani
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
authors.forename: M
authors.initials: M
authors.lastname: Carlà
authors.forename: M
authors.initials: M
authors.lastname: Olivotto
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured
chemical_list: D000081:Acetamides; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2; C014026:hexamethylene bisacetamide