Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations in vivo.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractOBJECTIVE: Constitutive activation of Stat5 has been observed in a variety of malignancies, particularly myeloid leukemias. To directly investigate the in vivo consequences of Stat5 perturbation, we expressed constitutively active forms in zebrafish. METHODS: We generated mutants of the zebrafish stat5.1 protein (N646H, H298R/N714F, and N714F) based on previously identified constitutively active mutants of murine Stat5a. The in vitro properties of these mutants were determined using phosphorylation-specific antibodies and luciferase reporter assays, and their in vivo effects were analyzed through microinjection of zebrafish embryos. RESULTS: Two of these stat5.1 mutants (N646H and H298R/N714F) showed increased tyrosine phosphorylation and transactivation activity compared to the wild-type protein. Expression of either mutant led to a range of hematological perturbations, which were more pronounced for the H298R/N714F mutant. Interestingly, expression of wild-type also produced generally similar phenotypes. Further analysis showed that expression of the H298R/N714F mutant led to increased numbers of early and late myeloid cells, erythrocytes, and B cells. Some nonhematopoietic developmental perturbations were also observed, but these were equally prominent with wild-type or mutant forms. CONCLUSION: These data implicate Stat5 activity as a direct critical regulator of hematological cell proliferation, suggesting a causal role for constitutively-active Stat5 in the etiology of hematological malignancies.
CitationExp. Hematol. 2006, 34 (2):179-87
DescriptionKEYWORDS - CLASSIFICATION: analysis;Amino Acid Substitution;Animals;Biology;cytology;Cell Line;Cell Lineage;Cell Proliferation;drug effects;etiology;genetics;Hematologic Diseases;Hematopoietic Stem Cells;Humans;metabolism;mechanisms of carcinogenesis;Molecular Biology;Mutagenesis,Site-Directed;Mutation;pathology;pharmacology;physiology;Phosphorylation;Proteins;Research;STAT5 Transcription Factor;Tyrosine;Zebrafish;Zebrafish Proteins.
- Constitutively active STAT5A and STAT5B in vitro and in vivo: mutation of STAT5 is not a frequent cause of leukemogenesis.
- Authors: Yamada K, Ariyoshi K, Onishi M, Miyajima A, Hayakawa F, Towatari M, Saito H, Oka Y, Asano S, Nosaka T, Kitamura T
- Issue date: 2000 Jan
- STAT5 requires the N-domain to maintain hematopoietic stem cell repopulating function and appropriate lymphoid-myeloid lineage output.
- Authors: Li G, Wang Z, Zhang Y, Kang Z, Haviernikova E, Cui Y, Hennighausen L, Moriggl R, Wang D, Tse W, Bunting KD
- Issue date: 2007 Nov
- Constitutive activation of Flt3 and STAT5A enhances self-renewal and alters differentiation of hematopoietic stem cells.
- Authors: Moore MA, Dorn DC, Schuringa JJ, Chung KY, Morrone G
- Issue date: 2007 Apr
- Constitutive STAT5 activation specifically cooperates with the loss of p53 function in B-cell lymphomagenesis.
- Authors: Joliot V, Cormier F, Medyouf H, Alcalde H, Ghysdael J
- Issue date: 2006 Aug 3
- A novel zebrafish jak2a(V581F) model shared features of human JAK2(V617F) polycythemia vera.
- Authors: Ma AC, Fan A, Ward AC, Liongue C, Lewis RS, Cheng SH, Chan PK, Yip SF, Liang R, Leung AY
- Issue date: 2009 Dec