Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor.
Inhibition of PRL hormone signaling by suppressor of cytokine signaling (SOCS)/cytokine-inducible SH2-containing protein (CIS) was investigated in transfected HEK 293 cells. We used the physiologically relevant wild-type beta-casein promoter as a target gene for PRL action. We demonstrate that CIS produces a 70% inhibition of PRL signaling by a mechanism ... distinct from, and downstream of, the effect of SOCS-1 on JAK2. This inhibition involves association with the PRL receptor (PRLR), resulting in the inhibition of signal transducer and activator of transcription 5 (STAT5) activation. Further, we show that SOCS-3 coimmunoprecipitates with the PRLR. These data suggest that SOCS-3 involves a second pathway for the inhibition of PRL signaling other than JAK2 inhibition. Additional results indicate that SOCS-2 can play a more important potentiator role on PRL signaling, resulting in a restoration of 50% of transcriptional inhibition induced by SOCS-3 and a restoration of 100% of transcriptional inhibition induced by CIS. SOCS-2 was able to block the inhibitory effect of SOCS-1. These results indicate that SOCS-2 seems to be an antagonist of the other SOCS. SOCS-1 binds JAK2 and inhibits its phosphorylation; SOCS-3 does not bind JAK2 but binds the PRLR that may mediate its inhibition of JAK2; and finally, CIS binds the PRLR but inhibits signal transducer and activator of transcription 5 rather than JAK2.
Mesh Terms:
Carrier Proteins, Caseins, Cell Line, DNA-Binding Proteins, Humans, Immediate-Early Proteins, Intracellular Signaling Peptides and Proteins, Janus Kinase 2, Milk Proteins, Phosphorylation, Prolactin, Promoter Regions, Genetic, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Receptors, Prolactin, Repressor Proteins, STAT5 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Trans-Activators, Transcription Factors, Tyrosine
Carrier Proteins, Caseins, Cell Line, DNA-Binding Proteins, Humans, Immediate-Early Proteins, Intracellular Signaling Peptides and Proteins, Janus Kinase 2, Milk Proteins, Phosphorylation, Prolactin, Promoter Regions, Genetic, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Receptors, Prolactin, Repressor Proteins, STAT5 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Trans-Activators, Transcription Factors, Tyrosine
Endocrinology
Date: Dec. 01, 2001
PubMed ID: 11713228
View in: Pubmed Google Scholar
Download Curated Data For This Publication
6558
Switch View:
- Interactions 2