Inhibition and Restoration of Prolactin Signal Transduction by Suppressors of Cytokine Signaling

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摘要：

Prolactin (PRL) has been shown to activate the cytoplasmic tyrosine kinase Janus kinase 2 (Jak2) and the subsequent recruitment of various signaling molecules including members of the signal transducer and activator of transcription family of transcription factors. Recently, an expanding family of cytokine-inducible inhibitors of signaling has been identified that initially included four members: suppressor of cytokine signaling (SOCS)-1, SOCS-2, SOCS-3, and cytokine-inducible src homology domain 2 (SH-2) proteins. The present study analyzes the role of these members in PRL signaling. Constitutive expression of SOCS-1 and SOCS-3 suppressed PRL-induced signal transducer and activator of transcription 5-dependent gene transcription, and Jak2 tyrosine kinase activity was greatly reduced in the presence of SOCS-1 or SOCS-3. SOCS-1 was shown to associate with Jak2, whereas SOCS-2 was associated with the prolactin receptor. Co-transfection studies were conducted to further analyze the interactions of SOCS proteins. SOCS-2 was shown to suppress the inhibitory effect of SOCS-1 by restoring Jak2 kinase activity but did not affect the inhibitory effect of SOCS-3 on PRL signaling. Northern blot analysis revealed that andgenes were transiently expressed in response to PRL, both and , whereas the expression of and genes was still elevated 24 h after hormonal stimulation. We thus propose that the early expressed genes (and) switch off PRL signaling and that the later expressed gene can restore the sensitivity of cells to PRL, partly by suppressing the SOCS-1 inhibitory effect.

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关键词：

plant physiology plant biochemistry

DOI：

10.1074/jbc.274.35.24497

被引量：

456

年份：

1999