Hanna Chan

• Huszenicza, Zsuzsa; Gilmour, Brian Christopher; Koll, Lise; Kjelstrup, Hanna; Chan, Hanna & Sundvold, Vibeke [Show all 8 contributors for this article] (2024). Interaction of T-cell-specific adapter protein with Src- and Tec-family kinases. Scandinavian Journal of Immunology. ISSN 0300-9475. doi: 10.1111/sji.13358.
• Borowicz, Pawel; Gjerstad, Vibeke Sundvold; Chan, Hanna; Abrahamsen, Greger; Kjelstrup, Hanna & Nyman, Tuula Anneli [Show all 7 contributors for this article] (2021). Tyr192 Regulates Lymphocyte-Specific Tyrosine Kinase Activity in T Cells. Journal of Immunology. ISSN 0022-1767. 207(4), p. 1128–1137. doi: 10.4049/jimmunol.2001105. Show summary

  TCR signaling critically depends on the tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase). Two phosphotyrosines, the activating pTyr394 and the inhibitory pTyr505, control Lck activity. Recently, pTyr192 in the Lck SH2 domain emerged as a third regulator. How pTyr192 may affect Lck function remains unclear. In this study, we explored the role of Lck Tyr192 using CRISPR/Cas9-targeted knock-in mutations in the human Jurkat T cell line. Our data reveal that both Lck pTyr394 and pTyr505 are controlled by Lck Tyr192. Lck with a nonphosphorylated SH2 domain (Lck Phe192) displayed hyperactivity, possibly by promoting Lck Tyr394 transphosphorylation. Lck Glu192 mimicking stable Lck pTyr192 was inhibited by Tyr505 hyperphosphorylation. To overcome this effect, we further mutated Tyr505. The resulting Lck Glu192/Phe505 displayed strongly increased amounts of pTyr394 both in resting and activated T cells. Our results suggest that a fundamental role of Lck pTyr192 may be to protect Lck pTyr394 and/or pTyr505 to maintain a pool of already active Lck in resting T cells. This provides an additional mechanism for fine-tuning of Lck as well as T cell activity.

• Borowicz, Pawel; Chan, Hanna; Hauge, Anette & Spurkland, Anne (2020). Adaptor proteins: Flexible and dynamic modulators of immune cell signalling. Scandinavian Journal of Immunology. ISSN 0300-9475. 92(6). doi: 10.1111/sji.12951. Full text in Research Archive Show summary

  To maintain homeostasis, all cells respond to environmental cues via a multitude of surface receptors. In order to act appropriately in their environment, cells are dependent on the transduction of the incoming signal through tightly regulated and interconnected signalling pathways to the cell nucleus. In particular, cells implicated in the immune system greatly depend on such systems to respond in a flexible and dynamic manner to environmental challenges. One major group of intracellular proteins that are involved in these signalling pathways are adaptor proteins. Although adaptor proteins are essential for normal immune cell operation, the functional role of this group of signalling proteins remains to be fully appreciated. So far, research on adaptor proteins has revealed their unique potential in building transient complexes in a reversible, dynamic and inducible manner. In this review, we explore the roles of adaptor proteins – in space and time of intracellular signalling – and their associations with human disease. Examples of adaptor proteins expressed in hematopoietic cells highlight their crucial role in the immune system. Lastly, we present challenges faced in elucidating roles of adaptor proteins, as illustrated by the T cell–specific adaptor (TSAd) protein encoded by the SH2D2A gene.

• Borowicz, Pawel; Chan, Hanna; Talmo Medina, Daniel; Gumpelmair, Simon; Kjelstrup, Hanna & Spurkland, Anne (2019). A simple and efficient workflow for generation of knock-in mutations in Jurkat T cells using CRISPR/Cas9. Scandinavian Journal of Immunology. ISSN 0300-9475. doi: 10.1111/sji.12862. Full text in Research Archive

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• Visser, Johan Georg; Borowicz, Pawel; Chan, Hanna; Hauge, Anette; Kjelstrup, Hanna & Spurkland, Anne (2023). Lck-SH2 domain superbinder for characterization of phosphotyrosine signaling in T-cell receptor pathway.
• Chan, Hanna; Berge, Tone; Grønningsæter, Ingrid Helene; Abbedissen, Ivan; Arnesen, Henriette & Birkeland, Signe [Show all 8 contributors for this article] (2023). Challenges of phenotype reproducibility in animal models: investigating the phenotype of TSAd knockout mice.
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Phuyal, Santosh; Lossius, Andreas & Spurkland, Anne (2023). β2, or not β2? Connecting the Lck-adaptor TSAd to integrin β2 via a combined wet lab & bioinformatic approach.
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Johan Georg, Visser; Lossius, Andreas & Spurkland, Anne (2022). Applying bioinformatics to pick-apart elusive protein functions: Focusing on TSAd/SH2D2A, an immune kinase adaptor.
• Chan, Hanna; Borowicz, Pawel; Kjelstrup, Hanna; Gilmour, Brian Christopher; Loza, Ivan Garcia & Stensland, Maria [Show all 8 contributors for this article] (2022). Novel interaction partners of the SH2 domain in T cell specific adaptor protein (TSAd).
• Borowicz, Pawel; Gopalakrishnan, Ramakrishna Prabhu; Chan, Hanna; Granum, Stine; Abrahamsen, Greger & Foss, Stian [Show all 9 contributors for this article] (2022). How to investigate the function of a single amino acid? Using the example of a conserved pTyr motif in the unstructured C-terminus of TSAd.
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Kjelstrup, Hanna & Spurkland, Anne (2021). Application of bioinformatics to outstanding questions in immunology: TSAd (T cell adapter protein).
• Borowicz, Pawel; Gopalakrishnan, Ramakrishna Prabhu; Chan, Hanna; Kjelstrup, Hanna; Foss, Stian & De Souza, Gustavo Antonio [Show all 8 contributors for this article] (2019). A conserved pTyr motif in the unstructured C-terminus regulates the function of the T cell specific adaptor TSAd.
• Borowicz, Pawel; Sundvold-Gjerstad, Vibeke; Chan, Hanna; Abrahamsen, Greger; Kjelstrup, Hanna & Medina, Daniel [Show all 8 contributors for this article] (2019). Tyr192 in the Lck SH2 domain affects the regulation of Lck activity.

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