HL-60 cells treated by @entity4515 develop the monocyte adherent phenotype and synthesize @entity2289 ( @entity2289 ). We focused our study on the identification of the @entity4515 -activated @entity7131 ( @entity7131 ) isoform and its downstream transduction pathway activating @entity2289 synthesis. Acquisition of the monocytic phenotype was evidenced by cell adherence (90-95%) and a sharp increase of @entity4210 for @entity10431 ( @entity10431 ) surface expression. Ro 31-8220, a specific inhibitor of @entity7131 , prevented @entity4515 -induced @entity2289 synthesis (mRNA and protein levels) and cell adhesion. To identify the @entity7131 isoform, we took advantage of the HL-525 cell line, an @entity1733 in @entity23001 gene expression. This defect prevents @entity4515 to induce the differentiation process. HL-525 stimulated by @entity4515 did not synthesize @entity2289 nor become adherent. However, in HL-525 cells either pretreated by @entity1968 that reinduces @entity23001 gene expression or transfected with @entity23001 cDNA, @entity4515 significantly activated @entity2289 synthesis and adhesion of cells. Immunoblotting of active Mitogen Activated Protein Kinase (MAPK) @entity3903 / @entity10368 in HL-60 cells showed a preferential and sustained activation of the @entity3903 isoform by @entity4515 over the @entity10368 isoform. Ro 31-8220 significantly attenuated this activation. @entity4286 and @entity5732 , both highly specific MEK inhibitors, efficiently prevented @entity4515 -induced @entity2289 synthesis (mRNA and protein levels) and cell adhesion whereas @entity1441 , a specific inhibitor of stress-activated MAPK p38, did not. Results obtained from HL-60 and HL-525 cells indicate that the @entity4515 -activated transduction pathway of @entity10431 expression involves a @entity7131 isoform other than @entity23001 . In conclusion, we propose that the pathway @entity23001 -MEK-MAPK @entity3903 is a potential linear route for @entity2289 synthesis leading to morphological changes and adherence linked to @entity4515 -induced differentiation in HL-60 cells.

Activation of @entity2289 synthesis by phorbol esters in human promyelocyte HL-60--roles of PCKbeta and MAPK XXXX .

@entity1733 :: ('MESH:C538324', 'Disease') :: ['HL-60 cell variant deficient'] @entity2289 :: ('5054', 'Gene') :: ['PAI-1', 'plasminogen activator inhibitor type-1'] @entity10431 :: ('5329', 'Gene') :: ['urokinase plasminogen activator', 'uPAR'] @entity23001 :: ('5579', 'Gene') :: ['PKCbeta'] @entity5732 :: ('MESH:C113580', 'Chemical') :: ['U0126'] @entity3903 :: ('23552', 'Gene') :: ['p42'] @entity4515 :: ('CHEBI:60755', 'Chemical') :: ['PMA'] @entity1441 :: ('MESH:C093642', 'Chemical') :: ['SB203580'] @entity7131 :: ('MESH:D020151', 'Disease') :: ['protein kinase C', 'PKC'] @entity10368 :: ('10561', 'Gene') :: ['p44'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD 098059'] @entity1968 :: ('MESH:D014212', 'Chemical') :: ['retinoic acid'] @entity4210 :: ('948', 'Gene') :: ['CD 36 and receptor']
@entity3903 :: (23552,Gene) :: ['p42']
