Artigo Acesso aberto Revisado por pares

IL-6 up-regulates Mcl-1 in human myeloma cells through JAK / STAT rather than Ras / MAP kinase pathway

1999; Wiley; Volume: 29; Issue: 12 Linguagem: Inglês

10.1002/(sici)1521-4141(199912)29

ISSN

1521-4141

Autores

Denis Puthier, Régis Bataille, Martine Amiot,

Tópico(s)

Protein Kinase Regulation and GTPase Signaling

Resumo

Mcl-1 is an anti-apoptotic member of the Bcl-2 family which is tightly regulated during myeloid and B cell differentiation. We have recently reported that Mcl-1 is expressed in human myeloma cells and that Mcl-1 and Bcl-xL expression are correlated. In the current study, we demonstrate that IL-6, a survival factor for the human myeloma cell line MDN, rapidly up-regulates Mcl-1 whereas it has no effect on Bcl-2 protein level. In MDN cells, IL-6 induces both extracellular signal-regulated protein kinase (ERK)1,2 and STAT3 activation whereas STAT1 and STAT5 activation remains undetectable. Furthermore, while investigating the IL-6 signaling pathway leading to Mcl-1 up-regulation, we show that a janus kinase (JAK)-2 inhibitor is able to inhibit both STAT3 activation and Mcl-1 up-regulation whereas an MAP/ERK kinase (MEK) inhibitor has no effect. In conclusion, our data suggest the involvement of the JAK / STAT pathway but not of the Ras / mitogen-activated protein (MAP) kinase pathway in IL-6-induced Mcl-1 up-regulation.

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