Physical and Functional Interactions between STAP-2/BKS and STAT5

Sekine, Yoshifumi; Yamamoto, T.; Yumioka, Taro; Sugiyama, Kenji; Tsuji, Satoshi; Oritani, Kenji; Shimoda, Kazuya; Minoguchi, Mayu; Yoshimura, Akihiko; Matsuda, Tadashi

doi:10.1074/jbc.m411692200

Cited by 58 publications

(95 citation statements)

References 48 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study we demonstrated that STAP-2 interacts with and modifies the function of various signaling or transcription molecules Yamamoto et al, 2003;Sekine et al, 2005Sekine et al, , 2006Sekine et al, , 2007bSekine et al, , 2009a. We also demonstrated that BCR-ABL acts as a novel binding partner for STAP-2 in the presence of both the STAP-2 SH2-like domain and STAP-2 Tyr250 phosphorylation.…”

Section: Discussionmentioning

confidence: 60%

“…BCR-ABL tyrosine kinase inhibitor, STI571 (imatinib mesylate), was kindly gifted by Novartis Pharmaceuticals (Basel, Switzerland). Expression vectors for p190/ p210BCR-ABL, ABL, STAP-2 and their mutants were described previously Toyofuku et al, 2004;Sekine et al, 2005;Tokunaga et al, 2010). Expression vectors for Myc-tagged-BCR was generated by PCR methods and sequenced (primer sequences are available upon request).…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

“…Its C-terminal region also has a proline-rich region and an YXXQ motif . Previous works in this laboratory found that STAP-2 have the ability to associate with and influence a variety of signaling or transcriptional molecules Yamamoto et al, 2003;Sekine et al, 2005Sekine et al, , 2006Sekine et al, , 2007bSekine et al, , 2009a, including the finding that STAP-2 can modulate the transcriptional activity of STAT3 and STAT5 Sekine et al, 2005), in addition to the FceRI and Toll-like receptor-mediated signals Sekine et al, 2006). Furthermore, thymocytes and peripheral T cells from STAP-2-deficient mice show enhanced interleukin-2 (IL-2)-or T cell receptor-dependent cell growth, integrin-mediated T-cell adhesion and impaired stromal cell-derived factor-1a (SDF-1a)-induced T-cell migration (Sekine et al, , 2007b(Sekine et al, , 2009a.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis

et al. 2012

View full text Add to dashboard Cite

In chronic myeloid leukemia (CML), the BCR-ABL fusion oncoprotein activates multiple pathways involved in cell survival, growth promotion and disease progression. In this report, we show that the signal transducing adaptor protein-2 (STAP-2) is involved in BCR-ABL activity. We demonstrate that STAP-2 bound to BCR-ABL, and BCR and ABL proteins, depending on the STAP-2 Src homology 2-like domain. BCR-ABL phosphorylates STAP-2 Tyr250 and the phosphorylated STAP-2 in turn up-regulated BCR-ABL phosphorylation, leading to enhanced activation of downstream signaling molecules including ERK, STAT5, BCL-xL and BCL-2. In addition, STAP-2 interacts with BCR-ABL to alter chemokine receptor expression leading to downregulation of CXCR4 and upregulation of CCR7. The interaction between STAP-2 and BCR-ABL plays a crucial role in conferring a growth advantage and resistance to imatinib, a BCR-ABL inhibitor, as well as tumor progression. Notably, mice injected with BCR-ABL/STAP-2-expressing Ba/F3 cells developed lymph node enlargement and hepatosplenomegaly. Moreover, suppression of STAP-2 in K562 CML cells resulted in no tumor formation in mice. Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity, and suggest that STAP-2 might be an important candidate for drug development for patients with CML. Further, the expression of STAP-2 provides useful information for estimating the characteristics of individual CML clones

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Reagents and Antibodiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Human embryonic kidney carcinoma cell line 293T, human hepatoma cell line Hep3B and human cervix carcinoma cell line HeLa were maintained in DMEM containing 10% FCS. Stable transformants expressing Myc-tagged STAP-2 in Jurkat [3], HeLa [13] and Hep3B [14] were established as described previously and maintained in the above medium in the presence of G418 (0.5 mg/ml). 293T was transfected by the standard calcium precipitation protocol.…”

Section: Cell Culture Transfection and Luciferase Assaysmentioning

confidence: 99%

“…Through these functional domains, STAP-2 can bind to a number of signaling molecules and regulate the activities of its binding partners. For example, STAP-2 interacts with STAT3 through its YXXQ motif [1] and with STAT5 through its PH and SH2-like domains [3], resulted in influencing their transcriptional activity. The SH2-like domain of STAP-2 binds to MyD88 and IKK-a/b, thereby modulating TLR4-mediated cytokine production and NFkB activation [4].…”

Section: Introductionmentioning

confidence: 99%

The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl

Sekine

Yamamoto

Ikeda

et al. 2009

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

Signal transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2 (SH2)-like domains as well as a YXXQ motif in its C-terminal region. Our previous study in T cells demonstrated that STAP-2 influences FAK protein levels through recruitment of E3 ubiquitin ligase, Cbl, to FAK.In the present study, we found that Cbl directly controls the protein levels and activity of STAP-2. STAP-2 physically interacted with Cbl through its PH and SH2-like domains.Small-interfering RNA-mediated reduction of endogenous Cbl restored STAP-2 protein levels. In contrast, over-expression of Cbl induced STAP-2 degradation. Importantly, Cbl-mediated regulation of STAP-2 protein levels affected Brk/STAP-2-induced STAT3 activation. These results indicate that Cbl regulates STAP-2 protein levels and Brk/STAP-2-mediated STAT3 activation.3

show abstract

STAP‐2 negatively regulates BCR‐mediated B cell activation by recruiting tyrosine‐protein kinase CSK to LYN

Kashiwakura,

Kawahara,

Inagaki

et al. 2023

FEBS Letters

Self Cite

View full text Add to dashboard Cite

Although signal‐transducing adaptor protein‐2 (STAP‐2) acts in certain immune responses, its role in B cell receptor (BCR)‐mediated signals remains unknown. In this study, we have revealed that BCR‐mediated signals, cytokine production and antibody production were increased in STAP‐2 knockout (KO) mice compared with wild‐type (WT) mice. Phosphorylation of tyrosine‐protein kinase LYN Y508 was reduced in STAP‐2 KO B cells after BCR stimulation. Mechanistic analysis revealed that STAP‐2 directly binds to LYN, dependently of STAP‐2 Y250 phosphorylation by LYN. Furthermore, phosphorylation of STAP‐2 enhanced interactions between LYN and tyrosine‐protein kinase CSK, resulting in enhanced CSK‐mediated LYN Y508 phosphorylation. These results suggest that STAP‐2 is crucial for controlling BCR‐mediated signals and antibody production by enhanced CSK‐mediated feedback regulation of LYN.

show abstract

Physical and Functional Interactions between STAP-2/BKS and STAT5

Cited by 58 publications

References 48 publications

STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis

STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis

The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl

STAP‐2 negatively regulates BCR‐mediated B cell activation by recruiting tyrosine‐protein kinase CSK to LYN

Contact Info

Product

Resources

About