Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b).
Mice lacking suppressor of cytokine signaling-2 (SOCS-2) exhibit accelerated postnatal growth resulting in adult mice that are 1.3 to 1.5 times the size of normal mice. In this study we examined the somatotrophic pathway to determine whether the production or actions of GH or IGF-I are altered in these mice. We demonstrated that SOCS-2(-/-) mice do not have elevated GH levels and suffer no major pituitary dysmorphogenesis, and that SOCS-2-deficient embryonic fibroblasts do not have altered IGF-I signaling. Primary hepatocytes from SOCS-2(-/-) mice, however, did have moderately prolonged signal transducer and activator of transcription 5 signaling in response to GH stimulation. Furthermore, the deletion of SOCS-2 from mice also lacking signal transducer and activator of transcription 5b had little effect on growth, suggesting that the action of SOCS-2 may be the regulation of the GH signaling pathway.
Greenhalgh
Christopher J
CJ
The Cooperative Research Centre for Cellular Growth Factors and the Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia. greenhalgh@wehi.edu.au
Bertolino
Patrick
P
Asa
Sylvia L
SL
Metcalf
Donald
D
Corbin
Jason E
JE
Adams
Timothy E
TE
Davey
Helen W
HW
Nicola
Nicos A
NA
Hilton
Douglas J
DJ
Alexander
Warren S
WS
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D006128:Growth / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins; D010766:Phosphorylation; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000473:pathology; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; C491409:Socs2 protein, mouse; C494096:Stat5b protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone