Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6.

The STAT family of proteins carries out a dual function: signal transduction and activation of transcription. A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor (EGF) and interleukin-6 (IL-6) but not interferon gamma (IFN-gamma). It is likely that this phosphoprotein forms homodimers as well as heterodimers with the first described member of the STAT family, Stat91 (renamed Stat1 alpha), which is activated by the IFNs and EGF. Differential activation of different STAT proteins in response to different ligands should help to explain specificity in nuclear signaling from the cell surface.

[1]  M. Greenberg,et al.  Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus. , 1993, Science.

[2]  M. Shibuya,et al.  Genistein, a specific inhibitor of tyrosine-specific protein kinases. , 1987, The Journal of biological chemistry.

[3]  R. Aebersold,et al.  The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Aebersold,et al.  Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Darnell,et al.  A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. , 1993, Science.

[6]  S. Cohen,et al.  Induction by EGF and interferon-gamma of tyrosine phosphorylated DNA binding proteins in mouse liver nuclei. , 1993, Science.

[7]  J. Darnell,et al.  Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. , 1992, Science.

[8]  J. Darnell,et al.  ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  N. Reich,et al.  Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4. , 1993, Science.

[10]  J. Darnell,et al.  Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. , 1992, Science.

[11]  J. Darnell,et al.  Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Darnell,et al.  Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons , 1991, Molecular and cellular biology.

[13]  Xin-Yuan Fu,et al.  Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter , 1993, Cell.

[14]  P. Heinrich,et al.  Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level , 1993, Molecular and cellular biology.

[15]  D. Levy,et al.  Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation. , 1993, Science.

[16]  C. Schindler,et al.  Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. , 1994, Science.

[17]  J. Darnell,et al.  A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. , 1993, Science.

[18]  D. S. Webb,et al.  Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. , 1993, Science.