STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif
| Autor: | Shigeru Minoguchi, Tadashi Matsuda, Daisuke Aki, Mayu Minoguchi, Akiko Joo, Taro Yumioka, Takashi Yamamoto, Akihiko Yoshimura |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
STAT3 Transcription Factor
Response element Mutant Amino Acid Motifs Molecular Sequence Data Biochemistry Mice Epidermal growth factor Animals Amino Acid Sequence RNA Messenger Phosphorylation STAT3 Acute-Phase Reaction Molecular Biology Adaptor Proteins Signal Transducing DNA Primers biology Base Sequence Sequence Homology Amino Acid Reverse Transcriptase Polymerase Chain Reaction Cell Membrane breakpoint cluster region Cell Biology Blotting Northern Phosphoproteins Molecular biology Precipitin Tests Pleckstrin homology domain DNA-Binding Proteins Gene Expression Regulation biology.protein Trans-Activators Tyrosine Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | The Journal of biological chemistry. 278(13) |
| ISSN: | 0021-9258 |
| Popis: | As a c-fms-interacting protein, we cloned a novel adaptor molecule, signal-transducing adaptor protein-2 (STAP-2), which contains pleckstrin homology- and Src homology 2-like (PH and SRC) domains and a proline-rich region. STAP-2 is structurally related to STAP-1/BRDG1 (BCR downstream signaling-1), which we had cloned previously from hematopoietic stem cells. STAP-2 is a murine homologue of a recently identified adaptor molecule, BKS, a substrate of BRK tyrosine kinase. STAP-2 was tyrosine-phosphorylated and translocated to the plasma membrane in response to epidermal growth factor when overexpressed in fibroblastic cells. To define the function of STAP-2, we generated mice lacking the STAP-2 gene. STAP-2 mRNA was strongly induced in the liver in response to lipopolysaccharide and in isolated hepatocytes in response to interleukin-6. In the STAP-2(-/-) hepatocytes, the interleukin-6-induced expression of acute-phase (AP) genes and the tyrosine-phosphorylation level of STAT3 were reduced specifically at the late phase (6-24 h) of the response. These data indicate that STAP-2 plays a regulatory role in the AP response in systemic inflammation. STAP-2 contains a YXXQ motif in the C-terminal region that is a potential STAT3-binding site. Overexpression of wild-type STAP-2, but not of mutants lacking this motif, enhanced the AP response element reporter activity and an AP protein production. These data suggest that STAP-2 is a new class of adaptor molecule that modulates STAT3 activity through its YXXQ motif. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|