SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell 1999 Sep 03;98(5):617-27
Date
09/18/1999Pubmed ID
10490101DOI
10.1016/s0092-8674(00)80049-5Scopus ID
2-s2.0-0033520389 293 CitationsAbstract
SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene-mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an embryonic lethality at 12-16 days associated with marked erythrocytosis. Moreover, the in vitro proliferative capacity of progenitors is greatly increased. SOCS3-deficient fetal liver stem cells can reconstitute hematopoiesis in lethally irradiated adults, indicating that its absence does not disturb bone marrow erythropoiesis. Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis.
Author List
Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JNAuthor
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDose-Response Relationship, Drug
Erythropoiesis
Flow Cytometry
Gene Expression Regulation, Developmental
Hematopoiesis
In Situ Hybridization
Interleukin-2
Interleukin-4
Liver
Mice
Mice, Mutant Strains
Models, Genetic
Mutagenesis
Phenotype
Proteins
Repressor Proteins
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Time Factors
Transcription Factors
Transfection
