Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains [1]. It has been identified as an enhancer of BMP-7 signaling, and it enhances BMP signaling by facilitating the binding of BMP7 to BMP receptor 1A [2][3]. KCP enhances BMP signaling by stabilizing BMP ligand-receptor interactions [4]. Additionally, KCP enhances BMP-7 activity by increasing BMP-7 binding to its receptor [5]. KCP stimulates BMP-7 signaling, and KCP-deficient mice have been found to be susceptible to developing renal interstitial fibrosis [6]. Furthermore, KCP enhances BMP/receptor interactions to increase the efficacy of signaling [7][8]. It has been suggested that KCP enhances the binding of the Bmp protein and its receptor by forming a tertiary complex [9]. KCP is similar in structure and function to a group of human complement inhibitors belonging to the family of regulators of complement activation (RCA) [10].
References:
[1] Y. Xu, "Kielin/chordin‐like protein deficiency aggravates pressure overload‐induced cardiac dysfunction and remodeling via p53/p21/ccnb1 signaling in mice", The Faseb Journal, vol. 38, no. 5, 2024. https://doi.org/10.1096/fj.202301841r
[2] R. Weiskirchen, "Bmp-7 as antagonist of organ fibrosis", Frontiers in Bioscience-Scholar, vol. 14, no. 1, p. 4992, 2009. https://doi.org/10.2741/3583
[3] A. Soofi, P. Zhang, & G. Dressler, "Kielin/chordin-like protein attenuates both acute and chronic renal injury", Journal of the American Society of Nephrology, vol. 24, no. 6, p. 897-905, 2013. https://doi.org/10.1681/asn.2012070759
[4] S. Bradford, E. Ranghini, E. Grimley, P. Lee, & G. Dressler, "High-throughput screens for agonists of bone morphogenetic protein (bmp) signaling identify potent benzoxazole compounds", Journal of Biological Chemistry, vol. 294, no. 9, p. 3125-3136, 2019. https://doi.org/10.1074/jbc.ra118.006817
[5] M. Zeisberg and R. Kalluri, "Reversal of experimental renal fibrosis by bmp7 provides insights into novel therapeutic strategies for chronic kidney disease", Pediatric Nephrology, vol. 23, no. 9, p. 1395-1398, 2008. https://doi.org/10.1007/s00467-008-0818-x
[6] A. Khwaja, M. Kossi, J. Floege, & M. Nahas, "The management of ckd: a look into the future", Kidney International, vol. 72, no. 11, p. 1316-1323, 2007. https://doi.org/10.1038/sj.ki.5002489
[7] J. Lin, S. Patel, M. Wang, & G. Dressler, "The cysteine-rich domain protein kcp is a suppressor of transforming growth factor β/activin signaling in renal epithelia", Molecular and Cellular Biology, vol. 26, no. 12, p. 4577-4585, 2006. https://doi.org/10.1128/mcb.02127-05
[8] A. Soofi, K. Wolf, M. Emont, N. Qi, G. Martinez-Santibañez, E. Grimleyet al., "The kielin/chordin-like protein (kcp) attenuates high-fat diet-induced obesity and metabolic syndrome in mice", Journal of Biological Chemistry, vol. 292, no. 22, p. 9051-9062, 2017. https://doi.org/10.1074/jbc.m116.771428
[9] M. Ikeya, M. Kawada, H. Kanazawa, N. Sasai, K. Nakao, Y. Furutaet al., "Essential pro-bmp roles of crossveinless 2 in mouse organogenesis", Development, vol. 133, no. 22, p. 4463-4473, 2006. https://doi.org/10.1242/dev.02647
[10] L. Mark, O. Spiller, M. Okroj, S. Chanas, J. Aitken, S. Wonget al., "Molecular characterization of the rhesus rhadinovirus (rrv) orf4 gene and the rrv complement control protein it encodes", Journal of Virology, vol. 81, no. 8, p. 4166-4176, 2007. https://doi.org/10.1128/jvi.02069-06
