Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses

被引:1044
作者
Teglund, S
McKay, C
Schuetz, E
van Deursen, JM
Stravopodis, D
Wang, DM
Brown, M
Bodner, S
Grosveld, G
Ihle, JN [1 ]
机构
[1] St Jude Childrens Res Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA
[3] St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA
[4] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA
[5] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA
[6] St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA
[7] Univ Tennessee, Sch Med, Dept Biochem, Memphis, TN 38105 USA
关键词
D O I
10.1016/S0092-8674(00)81444-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A variety of cytokines mediate the activation of Janus protein tyrosine kinases (Jaks). The Jaks then phosphorylate cellular substrates, including members of the signal transducers and activators of transcription (Stat) family of transcription factors. Among the Stats, the two highly related proteins, Stat5a and Stat5b, are activated by a variety of cytokines. To assess the role of the Stat5 proteins, mutant mice were derived that have the genes deleted individually or together. The phenotypes of the mice demonstrate an essential, and often redundant, role for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin. Conversely, the responses to a variety of cytokines that activate the Stat5 proteins, including erythropoietin, are largely unaffected.
引用
收藏
页码:841 / 850
页数:10
相关论文
共 62 条
  • [1] Angerer L. M., 1992, IN SITU HYBRIDIZATIO, P15
  • [2] [Anonymous], 1994, MANIPULATING MOUSE E
  • [3] Erythropoietin-induced erythroid differentiation of the human erythroleukemia cell line TF-1 correlates with impaired STAT5 activation
    Chretien, S
    Varlet, P
    Verdier, F
    Gobert, S
    Cartron, JP
    Gisselbrecht, S
    Mayeux, P
    Lacombe, C
    [J]. EMBO JOURNAL, 1996, 15 (16) : 4174 - 4181
  • [4] DISTRIBUTION OF THE MAMMALIAN STAT GENE FAMILY IN MOUSE CHROMOSOMES
    COPELAND, NG
    GILBERT, DJ
    SCHINDLER, C
    ZHONG, Z
    WEN, Z
    DARNELL, JE
    MUI, ALF
    MIYAJIMA, A
    QUELLE, FW
    IHLE, JN
    JENKINS, NA
    [J]. GENOMICS, 1995, 29 (01) : 225 - 228
  • [5] TYROSINE-343 IN THE ERYTHROPOIETIN RECEPTOR POSITIVELY REGULATES ERYTHROPOIETIN-INDUCED CELL-PROLIFERATION AND STAT5 ACTIVATION
    DAMEN, JE
    WAKAO, H
    MIYAJIMA, A
    KROSL, J
    HUMPHRIES, RK
    CUTLER, RL
    KRYSTAL, G
    [J]. EMBO JOURNAL, 1995, 14 (22) : 5557 - 5568
  • [6] JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS
    DARNELL, JE
    KERR, IM
    STARK, GR
    [J]. SCIENCE, 1994, 264 (5164) : 1415 - 1421
  • [7] STATs and gene regulation
    Darnell, JE
    [J]. SCIENCE, 1997, 277 (5332) : 1630 - 1635
  • [8] GROWTH-HORMONE DEFICIENCY IN LITTLE MICE RESULTS IN ABERRANT BODY-COMPOSITION, REDUCED INSULIN-LIKE GROWTH FACTOR-I AND INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 (IGFBP-3), BUT DOES NOT AFFECT IGFBP-2, IGFBP-1 OR IGFBP-4
    DONAHUE, LR
    BEAMER, WG
    [J]. JOURNAL OF ENDOCRINOLOGY, 1993, 136 (01) : 91 - 104
  • [9] Targeted disruption of the mouse STAT1 results in compromised innate immunity to viral disease
    Durbin, JE
    Hackenmiller, R
    Simon, MC
    Levy, DE
    [J]. CELL, 1996, 84 (03) : 443 - 450
  • [10] A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice
    Fero, ML
    Rivkin, M
    Tasch, M
    Porter, P
    Carow, CE
    Firpo, E
    Polyak, K
    Tsai, LH
    Broudy, V
    Perlmutter, RM
    Kaushansky, K
    Roberts, JM
    [J]. CELL, 1996, 85 (05) : 733 - 744