Sbk2-KO Mouse

Sbk2, SH3 domain binding kinase family member 2, encodes an evolutionarily conserved putative serine/threonine protein kinase. It is muscle-specific, highly atrium-enriched in neonatal and adult rats, and localizes around the A-band of cardiac sarcomeres. It plays a role in regulating atrial sarcomerogenesis, as its knockdown causes loss of sarcomeric organization in neonatal rat atrial myocytes (NRAMs) and their human counterparts, along with a decrease in sarcomeric gene expression [1].

In the context of tumor-related research, a 20-amino acid peptide (SBK2) recognizing the receptor protein-tyrosine phosphatase mu (PTPmu)-derived tumor-specific biomarker has been conjugated to different fluorophores for fluorescence image-guided surgery (FIGS). SBK2-ICG shows excellent specificity for gliomas in heterotopic tumors, while more hydrophilic dyes conjugated to SBK2 demonstrate no such specificity [2]. Additionally, the SBK2 peptide conjugated to a gadolinium chelate [SBK2-Tris-(Gd-DOTA)3] can label human glioma flank tumors in mice with high contrast, being a more specific MR molecular imaging probe than the current gold-standard reagent [3].

In summary, Sbk2 has a crucial function in maintaining sarcomere integrity in the atrium. In the tumor field, the SBK2 peptide targeting PTPmu shows promise for tumor imaging and potentially more complete tumor resection, providing new insights into both cardiac muscle development and tumor-related research.

References:

1. van Gorp, Pim R R, Zhang, Juan, Liu, Jia, Pijnappels, Daniël A, de Vries, Antoine A F. 2022. Sbk2, a Newly Discovered Atrium-Enriched Regulator of Sarcomere Integrity. In Circulation research, 131, 24-41. doi:10.1161/CIRCRESAHA.121.319300. https://pubmed.ncbi.nlm.nih.gov/35587025/

2. Johansen, Mette L, Vincent, Jason, Rose, Marissa, Sloan, Andrew E, Brady-Kalnay, Susann M. 2023. Comparison of Near-Infrared Imaging Agents Targeting the PTPmu Tumor Biomarker. In Molecular imaging and biology, 25, 744-757. doi:10.1007/s11307-023-01799-5. https://pubmed.ncbi.nlm.nih.gov/36695968/

3. Burden-Gulley, Susan M, Zhou, Zhuxian, Craig, Sonya El, Lu, Zheng-Rong, Brady-Kalnay, Susann M. 2013. Molecular Magnetic Resonance Imaging of Tumors with a PTPµ Targeted Contrast Agent. In Translational oncology, 6, 329-37. doi:. https://pubmed.ncbi.nlm.nih.gov/23730413/