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

Sekine, Yoshifumi; Yamamoto, Chihiro; Ikeda, Osamu; Muromoto, Ryuta; Nanbo, Asuka; Oritani, Kenji; Yoshimura, Akihiko; Matsuda, Tadashi

doi:10.1016/j.bbrc.2009.04.109

Cited by 16 publications

(20 citation statements)

References 22 publications

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“…17) Interestingly, it is also demonstrated that STAP-2 protein expression levels are also regulated by this proteasomal degradation. 18) These lines of evidence indicate that STAP-2 is a potential novel regulator of integrin/FAK-mediated T-cell adhesion (Fig. 5).…”

Section: Stap-2 Modulates T-cell Motilitymentioning

confidence: 89%

“…18) In the case of A431 cells, epidermal growth factor (EGF) induces rapid (5-10 min) translocation of green fluorescent protein (GFP)-fused STAP-2 wild type (WT) protein to the plasma membrane, while mutant STAP-2 that lacks Total RNA samples isolated from these tissues were subjected to quantitative real-time PCR analysis using STAP-1 and STAP-2 primers. Data represent the levels of these mRNA normalized to that of the GAPDH internal control.…”

Section: Reviewmentioning

confidence: 99%

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Adaptor Protein STAP-2 Modulates Cellular Signaling in Immune Systems

Sekine

2014

Biological & Pharmaceutical Bulletin

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Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains a pleckstrin homology (PH), Src homology 2 (SH2)-like domains, and proline-rich regions in its C-terminal. STAP-2 belongs to a family of STAP adaptor proteins and plays a crucial role in a variety of cellular signal transduction pathways by interacting with signaling or transcriptional molecules. STAP-2, in particular, regulates both the innate and adaptive immune systems. STAP-2 functionally interacts with signal transducers and activators of transcription 3 (STAT3) and STAT5 in cytokine signaling pathways. In addition, STAP-2 also binds to myeloid differentiation factor 88 (MyD88) and inhibitor (I)κB kinase α/β (IKK-α/β) in Toll-like receptor4 (TLR4) signaling, and enhances the production of inflammatory cytokines in macrophages. More importantly, experiments using STAP-2 deficient mice show that STAP-2 modulates several T-cell functions such as cell motility, survival and death. It is also reported that STAP-2 controls the immunoglobulin E (IgE)-mediated allergy response. This accumulated evidence indicates that adaptor protein STAP-2 is an important modulator of both the innate and adaptive immune systems.

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Section: Stap-2 Modulates T-cell Motilitymentioning

confidence: 89%

Section: Reviewmentioning

confidence: 99%

Adaptor Protein STAP-2 Modulates Cellular Signaling in Immune Systems

Sekine

2014

Biological & Pharmaceutical Bulletin

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“…STAT5a/b-deficient fetal liver hematopoietic progenitors fail to generate leukemia in recipient mice after retroviral transduction with BCR-ABL (Hoelbl et al, 2006). Among these BCR-ABL-related signaling molecules, we previously found that STAP-2 binds to and regulates c-CBL and STAT5 (Sekine et al, , 2009b. In particular, in a breast cancer model, STAP-2 was found to greatly enhance BRK-mediated STAT5 activation (Sekine et al, 2007b;Ikeda et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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

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“…The SH2-like domain also associates with many signaling molecules, including STAT5, myeloid differentiation factor 88, E3 ubiquitin ligase CBL, focal adhesion kinase and LMP1, as well as Vav1 [16,22,24,27,29,30,31,32]. In the cases of the association of STAP-2 with STAT5 and LMP1, both PH and SH2-like domains are involved.…”

Section: Discussionmentioning

confidence: 99%

STAP-2 interacts with Pyk2 and enhances Pyk2 activity in T-cells

Saitoh

Tsuchiya

Kashiwakura

et al. 2017

Biochemical and Biophysical Research Communications

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STAP-2 is an adaptor molecule regulating several signaling pathways, including TLRs and cytokine/chemokine receptors in immune cells. We previously reported that STAP-2 enhances SDF-1α-induced Vav1/Rac1-mediated T-cell chemotaxis. However, the detailed mechanisms of STAP-2 involvement in enhancing T-cell chemotaxis remain unknown. In the present study, we demonstrate that STAP-2 directly interacts with Pyk2, which is a key molecule in the regulation of SDF-1α/CXCR4-mediated T-cell chemotaxis, and increases phosphorylation of Pyk2. Pyk2 itself can induce STAP-2 Y250 phosphorylation, and this phosphorylation is critical for maximal interactions between STAP-2 and Pyk2. Finally, SDF-1α-induced T-cell chemotaxis is inhibited by treatment with Pyk2 siRNA or AG17, an inhibitor of Pyk2, in Jurkat cells overexpressing STAP-2. Taken together, the Pyk2/STAP-2 interaction is a novel mechanism to regulate SDF-1α-dependent T-cell chemotaxis.

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

Cited by 16 publications

References 22 publications

Adaptor Protein STAP-2 Modulates Cellular Signaling in Immune Systems

Adaptor Protein STAP-2 Modulates Cellular Signaling in Immune Systems

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

STAP-2 interacts with Pyk2 and enhances Pyk2 activity in T-cells

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