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STAT5B (signal transducer and activator of transcription 5B)

Identity

Other namesSTAT5
HGNC (Hugo) STAT5B
LocusID (NCBI) 6777
Location 17q21.2
Location_base_pair Starts at 40351195 and ends at 40428424 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  The STAT5b gene. The STAT5b gene is composed of 19 exons that are transcribed as a 5090 nucleotide RNA transcript. The RNA is translated into the STAT5b protein containing 787 amino acids.
Description The STAT5b gene is composed of 77229 base pairs and contains 19 exons. As exon 1 contains only the 5' UTR, there are 18 coding exons. The mRNA is composed of 5090 base pairs.
Transcription There is one major transcript.

Protein

Note STAT5b is composed of 787 amino acids (92 kD).
 
  Schematic of the STAT5b protein. The STAT5b protein contains several conserved domains: the coiled-coil domain, the DNA binding domain, the SH2 domain, and the carboxy-terminal transactivation domain. While phosphorylation of Y699 is required for transcriptional activity, there are multiple tyrosine and serine phosphorylation sites that have been identified under specific conditions and in certain cell types.
Description STAT5b is a member of the signal transducer and activator of transcription (STAT) family. The STAT proteins contain several conserved domains: the coiled-coil domain, the DNA binding domain, the SH2 domain, and the carboxy-terminal transactivation domain. STATs remain latent in the cytoplasm until the binding of a cytokine or growth factor to its receptor, resulting in recruitment of the STAT to the ligand receptor complex (Levy and Darnell, 2002; Herrington et al., 1999; Heim et al., 1995). The STAT protein is then phosphorylated by receptor tyrosine kinases or non-receptor tyrosine kinases, such as Janus kinases (JAKs) and Src family members. This phosphorylation results in SH2 domain mediated dimerization of STATs and their translocation to the nucleus. In the nucleus, STAT dimers bind to consensus DNA sequences and recruit additional transcription machinery to initiate specific gene regulation. To date, seven members of the STAT family have been identified (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) (Silva, 2004; Calò et al., 2003; Moriggl et al., 1996; Liu et al., 1996; Liu et al., 1997).
STAT5b is activated by a variety of stimuli, including interleukins, erythropoietin, growth hormone (GH), prolactin (Prl), and epidermal growth factor (EGF). Activation of STAT5b results in phosphorylation of tyrosine 699. Phosphorylation of this tyrosine is required for DNA binding and transcriptional activity. Mutation of Y699 of STAT5b inhibits stimulant-induced tyrosine phosphorylation, DNA binding, and transcriptional activity (Gebert et al., 1997; Gouilleux et al., 1994; Kloth et al., 2003). Additional tyrosine phosphorylation sites (Y679, Y725, Y740, and Y743) and serine phosphorylation sites (S715, S731) have been shown to alter STAT5b transcriptional activity (Kloth et al., 2002; Weaver and Silva, 2006; Yamashita et al., 2001; Park et al., 2001; Decker and Kovarik, 2000).
While no classic nuclear localization signal (NLS) composed of a cluster of basic amino acids has been reported for the STAT5b, the STAT5b dimer is actively translocated through the nuclear pore complex and accumulates in the nucleus upon phosphorylation (Xu and Massagué, 2004).
STAT5b can be negatively regulated by phosphatase-mediated dephosphorylation, ubiquitination-promoting proteosome degradation, or by negative feedback loops.
Expression Ubiquitous.
Localisation STAT5b is localized in the cytoplasm and translocates to the nucleus upon phosphorylation of Y699. However, unphosphorylated STAT5b has also been reported to be found in the nucleus (Brown and Zeidler, 2008; Iyer and Reich, 2008; Zeng et al., 2002).
Function Transcription factor. STAT5b mediates the transcription of numerous genes in various cell signaling pathways involved in cellular proliferation, differentiation, and cell survival. The STATs bind TTC(N3)GAA gamma-interferon-activating sequence (GAS) sites in the promoters of target genes.
Homology Shares homology with the other STAT family members (STAT1, 2, 3, 4, 5a, and 6). Additionally, STAT5a and STAT5b are 94% similar at the amino acid level, differing primarily at the C-terminus (Teglund et al., 1998; Silva et al., 1996; Lin et al., 1996; Liu et al., 1995).

Mutations

Note To date, there are 6 reported cases of humans having a mutant STAT5b, and these cases result from five different STAT5b mutations. The first STAT5b mutation in a human to be reported was the A630P STAT5b mutant. This single point mutation in the SH2 domain causes missfolding of STAT5b. A nonsense mutation in the coiled-coil domain (R152X) results in the absence of detectable STAT5b protein. Insertion of a nucleotide in the DBD at position 1102 (Q368fsX376) or 1191 (N398E) causes a frameshift mutation resulting in a non-functional truncated STAT5b. Likewise, a single nucleotide deletion in the linker domain at position 1680 (E561R) also results in a truncated STAT5b. In each of the 6 cases, STAT5b protein is not detectable, but STAT5a protein levels are unchanged. These reports are from homozygous patients while the parents are heterozygous for the STAT5b mutation and display a normal phenotype. The phenotype of each STAT5b mutant is similar: pronounced short stature, growth hormone insensitivity despite normal to high levels of GH in the serum, and extremely low IGF-I and IGFBP-3 levels (Chia et al., 2006; Hwa et al., 2007; Nadeau et al., 2011).

Implicated in

Entity Solid tumors
Note STAT5b is implicated in prostate cancer (Koptyra et al., 2011; Clevenger, 2004), breast cancer (Bernaciak et al., 2009; Peck et al., 2011; Strauss et al., 2006; Sultan et al., 2005; Yamashita et al., 2003), lung cancer (Sánchez-Ceja et al., 2006), head and neck cancer (Koppikar et al., 2008), ovarian cancer (Chen et al., 2004), hepatocellular carcinoma (Lee et al., 2006), cervical cancer (Lopez et al., 2011), and colorectal cancer (Du et al., 2011).
  
Entity Leukemias and lymphomas
Note STAT5b is involved in the proliferation of chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cells (Baśkiewicz-Masiuk and Machalińkski, 2004; Sternberg and Gilliland, 2004; Hoover et al., 2001; de Groot et al., 1999). Additionally, STAT5b has been found to fuse with the retinoic acid receptor-alpha (RARalpha) gene in a subset of acute promyelocytic leukemias (APLL) (Arnould et al., 1999). Furthermore, STAT5b plays a role in the development of lymphoblastic lymphoma (Bessette et al., 2008; Nieborowska-Skorska et al., 2001).
  
Entity Laron type dwarfism II
Note Laron type dwarfism II (LTD2) is mediated by defects in STAT5b (Nadeau et al., 2011; Freeth et al., 1998; Chia et al., 2006).
  
Entity Graft-versus-host disease
Note Constitutively active STAT5b increases expansion of regulatory T cells (Treg), and these Tregs are more potent suppressors of graft-versus-host disease in vivo, compared to wild-type Tregs (Vogtenhuber et al., 2010).
  
Entity Crohn's disease/colitis
Note Growth hormone reduces mucosal inflammation in colitis by activating STAT5b, such that STAT5b deficient mice demonstrated more severe colitis compared to wild-type mice (Han et al., 2006).
  
Entity Diabetes and metabolic disorder
Note Upon leptin stimulation, the leptin receptor can mediate STAT5b tyrosine phosphorylation and transcriptional activity in the liver, gastrointestinal tract, and brain (Mütze et al., 2007; Ghilardi et al., 1996; Gong et al., 2007).
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029

External links

Nomenclature
HGNC (Hugo)STAT5B   11367
Cards
AtlasSTAT5BID217ch17q21
Entrez_Gene (NCBI)STAT5B  6777  signal transducer and activator of transcription 5B
GeneCards (Weizmann)STAT5B
Ensembl (Hinxton)ENSG00000173757 [Gene_View]  chr17:40351195-40428424 [Contig_View]  STAT5B [Vega]
ICGC DataPortalENSG00000173757
AceView (NCBI)STAT5B
Genatlas (Paris)STAT5B
WikiGenes6777
SOURCE (Princeton)NM_012448
Genomic and cartography
GoldenPath (UCSC)STAT5B  -  17q21.2   chr17:40351195-40428424 -  17q11.2   [Description]    (hg19-Feb_2009)
EnsemblSTAT5B - 17q11.2 [CytoView]
Mapping of homologs : NCBISTAT5B [Mapview]
OMIM245590   604260   
Gene and transcription
Genbank (Entrez)AB208920 AK308163 AL040162 AL080218 BC020868
RefSeq transcript (Entrez)NM_012448
RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_007271 NT_010783 NW_001838436 NW_004929407
Consensus coding sequences : CCDS (NCBI)STAT5B
Cluster EST : UnigeneHs.595276 [ NCBI ]
CGAP (NCI)Hs.595276
Alternative Splicing : Fast-db (Paris)GSHG0013418
Alternative Splicing GalleryENSG00000173757
Gene ExpressionSTAT5B [ NCBI-GEO ]     STAT5B [ SEEK ]   STAT5B [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP51692 (Uniprot)
NextProtP51692  [Medical]
With graphics : InterProP51692
Splice isoforms : SwissVarP51692 (Swissvar)
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)   
Domains : Interpro (EBI)EF-hand-dom_pair    p53-like_TF_DNA-bd    SH2    STAT    STAT_TF_alpha    STAT_TF_coiled-coil    STAT_TF_DNA-bd    STAT_TF_DNA-bd_sub    STAT_TF_prot_interaction   
Related proteins : CluSTrP51692
Domain families : Pfam (Sanger)SH2 (PF00017)    STAT_alpha (PF01017)    STAT_bind (PF02864)    STAT_int (PF02865)   
Domain families : Pfam (NCBI)pfam00017    pfam01017    pfam02864    pfam02865   
Domain families : Smart (EMBL)SH2 (SM00252)  STAT_int (SM00964)  
DMDM Disease mutations6777
Blocks (Seattle)P51692
Human Protein AtlasENSG00000173757
Peptide AtlasP51692
HPRD05037
IPIIPI00103415   IPI00878127   
Protein Interaction databases
DIP (DOE-UCLA)P51692
IntAct (EBI)P51692
FunCoupENSG00000173757
BioGRIDSTAT5B
IntegromeDBSTAT5B
STRING (EMBL)STAT5B
Ontologies - Pathways
QuickGOP51692
Ontology : AmiGOallantoin metabolic process  RNA polymerase II core promoter sequence-specific DNA binding  luteinization  response to hypoxia  natural killer cell differentiation  liver development  chromatin binding  double-stranded DNA binding  sequence-specific DNA binding transcription factor activity  signal transducer activity  calcium ion binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  citrate metabolic process  2-oxoglutarate metabolic process  succinate metabolic process  oxaloacetate metabolic process  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  isoleucine metabolic process  valine metabolic process  creatine metabolic process  fatty acid metabolic process  acute-phase response  JAK-STAT cascade  female pregnancy  lactation  regulation of steroid metabolic process  taurine metabolic process  protein phosphatase binding  lipid storage  regulation of cell adhesion  regulation of epithelial cell differentiation  response to estradiol  response to lipopolysaccharide  positive regulation of natural killer cell proliferation  positive regulation of natural killer cell differentiation  cellular response to hormone stimulus  T cell differentiation in thymus  glucocorticoid receptor binding  prolactin signaling pathway  regulation of multicellular organism growth  positive regulation of multicellular organism growth  positive regulation of activated T cell proliferation  progesterone metabolic process  T cell homeostasis  negative regulation of apoptotic process  positive regulation of interleukin-2 biosynthetic process  response to ethanol  positive regulation of B cell differentiation  positive regulation of gamma-delta T cell differentiation  negative regulation of erythrocyte differentiation  positive regulation of mitotic cell cycle  positive regulation of transcription from RNA polymerase II promoter  positive regulation of natural killer cell mediated cytotoxicity  creatinine metabolic process  development of secondary female sexual characteristics  development of secondary male sexual characteristics  protein dimerization activity  Peyer's patch development  positive regulation of smooth muscle cell proliferation  positive regulation of inflammatory response  positive regulation of cellular component movement  JAK-STAT cascade involved in growth hormone signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  response to interleukin-2  response to interleukin-4  response to interleukin-15  cellular response to growth factor stimulus  cellular response to epidermal growth factor stimulus  
Ontology : EGO-EBIallantoin metabolic process  RNA polymerase II core promoter sequence-specific DNA binding  luteinization  response to hypoxia  natural killer cell differentiation  liver development  chromatin binding  double-stranded DNA binding  sequence-specific DNA binding transcription factor activity  signal transducer activity  calcium ion binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  citrate metabolic process  2-oxoglutarate metabolic process  succinate metabolic process  oxaloacetate metabolic process  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  isoleucine metabolic process  valine metabolic process  creatine metabolic process  fatty acid metabolic process  acute-phase response  JAK-STAT cascade  female pregnancy  lactation  regulation of steroid metabolic process  taurine metabolic process  protein phosphatase binding  lipid storage  regulation of cell adhesion  regulation of epithelial cell differentiation  response to estradiol  response to lipopolysaccharide  positive regulation of natural killer cell proliferation  positive regulation of natural killer cell differentiation  cellular response to hormone stimulus  T cell differentiation in thymus  glucocorticoid receptor binding  prolactin signaling pathway  regulation of multicellular organism growth  positive regulation of multicellular organism growth  positive regulation of activated T cell proliferation  progesterone metabolic process  T cell homeostasis  negative regulation of apoptotic process  positive regulation of interleukin-2 biosynthetic process  response to ethanol  positive regulation of B cell differentiation  positive regulation of gamma-delta T cell differentiation  negative regulation of erythrocyte differentiation  positive regulation of mitotic cell cycle  positive regulation of transcription from RNA polymerase II promoter  positive regulation of natural killer cell mediated cytotoxicity  creatinine metabolic process  development of secondary female sexual characteristics  development of secondary male sexual characteristics  protein dimerization activity  Peyer's patch development  positive regulation of smooth muscle cell proliferation  positive regulation of inflammatory response  positive regulation of cellular component movement  JAK-STAT cascade involved in growth hormone signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  response to interleukin-2  response to interleukin-4  response to interleukin-15  cellular response to growth factor stimulus  cellular response to epidermal growth factor stimulus  
Pathways : BIOCARTAIL22 Soluble Receptor Signaling [Genes]    IL 3 signaling pathway [Genes]    IL-7 Signal Transduction [Genes]    EPO Signaling Pathway [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]    Inhibition of Cellular Proliferation by Gleevec [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    TPO Signaling Pathway [Genes]    Growth Hormone Signaling Pathway [Genes]    IL 2 signaling pathway [Genes]   
Pathways : KEGGErbB signaling pathway    Chemokine signaling pathway    Jak-STAT signaling pathway    Prolactin signaling pathway    Hepatitis B    Measles    HTLV-I infection    Pathways in cancer    Viral carcinogenesis    Chronic myeloid leukemia    Acute myeloid leukemia   
REACTOMEP51692 [protein]
REACTOME PathwaysREACT_116125 Disease [pathway]
REACTOME PathwaysREACT_6900 Immune System [pathway]
REACTOME PathwaysREACT_111102 Signal Transduction [pathway]
Protein Interaction DatabaseSTAT5B
Wikipedia pathwaysSTAT5B
Gene fusion - rearrangments
Rearrangement : TICdbSTAT5B [17q21.2]  -  RARA [-]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)STAT5B
SNP (GeneSNP Utah)STAT5B
SNP : HGBaseSTAT5B
Genetic variants : HAPMAPSTAT5B
1000_GenomesSTAT5B 
ICGC programENSG00000173757 
Cancer Gene: CensusSTAT5B 
CONAN: Copy Number AnalysisSTAT5B 
Somatic Mutations in Cancer : COSMICSTAT5B 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
DECIPHER (Syndromes)17:40351195-40428424
Mutations and Diseases : HGMDSTAT5B
OMIM245590    604260   
MedgenSTAT5B
GENETestsSTAT5B
Disease Genetic AssociationSTAT5B
Huge Navigator STAT5B [HugePedia]  STAT5B [HugeCancerGEM]
Genomic VariantsSTAT5B  STAT5B [DGVbeta]
Exome VariantSTAT5B
dbVarSTAT5B
ClinVarSTAT5B
snp3D : Map Gene to Disease6777
General knowledge
Homologs : HomoloGeneSTAT5B
Homology/Alignments : Family Browser (UCSC)STAT5B
Phylogenetic Trees/Animal Genes : TreeFamSTAT5B
Chemical/Protein Interactions : CTD6777
Chemical/Pharm GKB GenePA36186
Clinical trialSTAT5B
Cancer Resource (Charite)ENSG00000173757
Other databases
Probes
Litterature
PubMed224 Pubmed reference(s) in Entrez
CoreMineSTAT5B
GoPubMedSTAT5B
iHOPSTAT5B

Bibliography

Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription.
Gouilleux F, Wakao H, Mundt M, Groner B.
EMBO J. 1994 Sep 15;13(18):4361-9.
PMID 7925280
 
Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway.
Heim MH, Kerr IM, Stark GR, Darnell JE Jr.
Science. 1995 Mar 3;267(5202):1347-9.
PMID 7871432
 
Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue.
Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L.
Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8831-5.
PMID 7568026
 
Defective STAT signaling by the leptin receptor in diabetic mice.
Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6231-5.
PMID 8692797
 
Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells.
Lin JX, Mietz J, Modi WS, John S, Leonard WJ.
J Biol Chem. 1996 May 3;271(18):10738-44.
PMID 8631883
 
Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation.
Liu X, Robinson GW, Hennighausen L.
Mol Endocrinol. 1996 Dec;10(12):1496-506.
PMID 8961260
 
Deletion of the carboxyl-terminal transactivation domain of MGF-Stat5 results in sustained DNA binding and a dominant negative phenotype.
Moriggl R, Gouilleux-Gruart V, Jahne R, Berchtold S, Gartmann C, Liu X, Hennighausen L, Sotiropoulos A, Groner B, Gouilleux F.
Mol Cell Biol. 1996 Oct;16(10):5691-700.
PMID 8816482
 
Characterization and cloning of STAT5 from IM-9 cells and its activation by growth hormone.
Silva CM, Lu H, Day RN.
Mol Endocrinol. 1996 May;10(5):508-18.
PMID 8732682
 
Regulation of signal transducer and activator of transcription (STAT) 5b activation by the temporal pattern of growth hormone stimulation.
Gebert CA, Park SH, Waxman DJ.
Mol Endocrinol. 1997 Apr;11(4):400-14.
PMID 9092792
 
Stat5a is mandatory for adult mammary gland development and lactogenesis.
Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L.
Genes Dev. 1997 Jan 15;11(2):179-86.
PMID 9009201
 
Activation of the signal transducers and activators of transcription signaling pathway by growth hormone (GH) in skin fibroblasts from normal and GH binding protein-positive Laron Syndrome children.
Freeth JS, Silva CM, Whatmore AJ, Clayton PE.
Endocrinology. 1998 Jan;139(1):20-8.
PMID 9421393
 
Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses.
Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN.
Cell. 1998 May 29;93(5):841-50.
PMID 9630227
 
STAT5 activation by BCR-Abl contributes to transformation of K562 leukemia cells.
de Groot RP, Raaijmakers JA, Lammers JW, Jove R, Koenderman L.
Blood. 1999 Aug 1;94(3):1108-12.
PMID 10419904
 
A functional DNA binding domain is required for growth hormone-induced nuclear accumulation of Stat5B.
Herrington J, Rui L, Luo G, Yu-Lee LY, Carter-Su C.
J Biol Chem. 1999 Feb 19;274(8):5138-45.
PMID 9988763
 
Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression.
Yamashita H, Nevalainen MT, Xu J, LeBaron MJ, Wagner KU, Erwin RA, Harmon JM, Hennighausen L, Kirken RA, Rui H.
Mol Cell Endocrinol. 2001 Oct 25;183(1-2):151-63.
PMID 11604235
 
The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia.
Arnould C, Philippe C, Bourdon V, Gr goire MJ, Berger R, Jonveaux P.
Hum Mol Genet. 1999 Sep;8(9):1741-9.
PMID 10441338
 
Serine phosphorylation of STATs.
Decker T, Kovarik P.
Oncogene. 2000 May 15;19(21):2628-37. (REVIEW)
PMID 10851062
 
Cooperative and redundant effects of STAT5 and Ras signaling in BCR/ABL transformed hematopoietic cells.
Hoover RR, Gerlach MJ, Koh EY, Daley GQ.
Oncogene. 2001 Sep 13;20(41):5826-35.
PMID 11593388
 
Role of signal transducer and activator of transcription 5 in nucleophosmin/ anaplastic lymphoma kinase-mediated malignant transformation of lymphoid cells.
Nieborowska-Skorska M, Slupianek A, Xue L, Zhang Q, Raghunath PN, Hoser G, Wasik MA, Morris SW, Skorski T.
Cancer Res. 2001 Sep 1;61(17):6517-23.
PMID 11522649
 
Serine phosphorylation of GH-activated signal transducer and activator of transcription 5a (STAT5a) and STAT5b: impact on STAT5 transcriptional activity.
Park SH, Yamashita H, Rui H, Waxman DJ.
Mol Endocrinol. 2001 Dec;15(12):2157-71.
PMID 11731617
 
Novel activation of STAT5b in response to epidermal growth factor.
Kloth MT, Catling AD, Silva CM.
J Biol Chem. 2002 Mar 8;277(10):8693-701. Epub 2001 Dec 20.
PMID 11751923
 
Stats: transcriptional control and biological impact.
Levy DE, Darnell JE Jr.
Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62. (REVIEW)
PMID 12209125
 
Stat5B shuttles between cytoplasm and nucleus in a cytokine-dependent and -independent manner.
Zeng R, Aoki Y, Yoshida M, Arai K, Watanabe S.
J Immunol. 2002 May 1;168(9):4567-75.
PMID 11971004
 
STAT proteins: from normal control of cellular events to tumorigenesis.
Calo V, Migliavacca M, Bazan V, Macaluso M, Buscemi M, Gebbia N, Russo A.
J Cell Physiol. 2003 Nov;197(2):157-68. (REVIEW)
PMID 14502555
 
STAT5b, a Mediator of Synergism between c-Src and the Epidermal Growth Factor Receptor.
Kloth MT, Laughlin KK, Biscardi JS, Boerner JL, Parsons SJ, Silva CM.
J Biol Chem. 2003 Jan 17;278(3):1671-9. Epub 2002 Nov 11.
PMID 12429742
 
Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells.
Yamashita H, Iwase H, Toyama T, Fujii Y.
Oncogene. 2003 Mar 20;22(11):1638-52.
PMID 12642867
 
The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells.
Baskiewicz-Masiuk M, Machalinski B.
Eur J Haematol. 2004 Jun;72(6):420-9.
PMID 15128421
 
VEGF, VEGFRs expressions and activated STATs in ovarian epithelial carcinoma.
Chen H, Ye D, Xie X, Chen B, Lu W.
Gynecol Oncol. 2004 Sep;94(3):630-5.
PMID 15350351
 
Roles and regulation of stat family transcription factors in human breast cancer.
Clevenger CV.
Am J Pathol. 2004 Nov;165(5):1449-60. (REVIEW)
PMID 15509516
 
Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis.
Silva CM.
Oncogene. 2004 Oct 18;23(48):8017-23. (REVIEW)
PMID 15489919
 
The role of signal transducer and activator of transcription factors in leukemogenesis.
Sternberg DW, Gilliland DG.
J Clin Oncol. 2004 Jan 15;22(2):361-71. (REVIEW)
PMID 14722044
 
Nucleocytoplasmic shuttling of signal transducers.
Xu L, Massague J.
Nat Rev Mol Cell Biol. 2004 Mar;5(3):209-19. (REVIEW)
PMID 14991001
 
Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells.
Sultan AS, Xie J, LeBaron MJ, Ealley EL, Nevalainen MT, Rui H.
Oncogene. 2005 Jan 27;24(5):746-60.
PMID 15592524
 
Aberrant folding of a mutant Stat5b causes growth hormone insensitivity and proteasomal dysfunction.
Chia DJ, Subbian E, Buck TM, Hwa V, Rosenfeld RG, Skach WR, Shinde U, Rotwein P.
J Biol Chem. 2006 Mar 10;281(10):6552-8. Epub 2005 Nov 22.
PMID 16303763
 
Signal transducer and activator of transcription 5b promotes mucosal tolerance in pediatric Crohn's disease and murine colitis.
Han X, Osuntokun B, Benight N, Loesch K, Frank SJ, Denson LA.
Am J Pathol. 2006 Dec;169(6):1999-2013.
PMID 17148664
 
Signal transducers and activators of transcription 5b activation enhances hepatocellular carcinoma aggressiveness through induction of epithelial-mesenchymal transition.
Lee TK, Man K, Poon RT, Lo CM, Yuen AP, Ng IO, Ng KT, Leonard W, Fan ST.
Cancer Res. 2006 Oct 15;66(20):9948-56.
PMID 17047057
 
Differential expression of STAT5 and Bcl-xL, and high expression of Neu and STAT3 in non-small-cell lung carcinoma.
Sanchez-Ceja SG, Reyes-Maldonado E, Vazquez-Manriquez ME, Lopez-Luna JJ, Belmont A, Gutierrez-Castellanos S.
Lung Cancer. 2006 Nov;54(2):163-8. Epub 2006 Sep 7.
PMID 16959370
 
STAT 5a expression in the breast is maintained in secretory carcinoma, in contrast to other histologic types.
Strauss BL, Bratthauer GL, Tavassoli FA.
Hum Pathol. 2006 May;37(5):586-92.
PMID 16647957
 
Modulation of signal transducer and activator of transcription 5b activity in breast cancer cells by mutation of tyrosines within the transactivation domain.
Weaver AM, Silva CM.
Mol Endocrinol. 2006 Oct;20(10):2392-405. Epub 2006 Jun 13.
PMID 16772534
 
The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms.
Gong Y, Ishida-Takahashi R, Villanueva EC, Fingar DC, Munzberg H, Myers MG Jr.
J Biol Chem. 2007 Oct 19;282(42):31019-27. Epub 2007 Aug 28.
PMID 17726024
 
Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene.
Hwa V, Camacho-Hubner C, Little BM, David A, Metherell LA, El-Khatib N, Savage MO, Rosenfeld RG.
Horm Res. 2007;68(5):218-24. Epub 2007 Mar 28.
PMID 17389811
 
Nuclear translocation of the transcription factor STAT5 in the rat brain after systemic leptin administration.
Mutze J, Roth J, Gerstberger R, Hubschle T.
Neurosci Lett. 2007 May 7;417(3):286-91. Epub 2007 Mar 2.
PMID 17353091
 
A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling.
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Contributor(s)

Written08-2011Amanda M Del Rosario, Teresa M Bernaciak, Corinne M Silva
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA (AMDR); NIAID/NIH/DHHS, 6610 Rockledge Drive, Bethesda, MD 20817, USA (TMB); DEM/NIDDK/NIH, 6707 Democracy Blvd, Bethesda, MD 20892, USA (CMS)

Citation

This paper should be referenced as such :
Del, Rosario AM ; Bernaciak, TM ; Silva, CM
STAT5B (signal transducer and activator of transcription 5B)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):106-110.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/STAT5BID217ch17q21.html

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