BMPR2

Case Study 1: Laia Bonjoch, 2023

Colorectal cancer (CRC) is one of the most prevalent tumors worldwide, with incidence quickly increasing (particularly in the context of early-onset cases), despite important prevention efforts, mainly in the form of population-wide screening programs. Although many cases present a clear familial component, the current list of hereditary CRC genes leaves a considerable proportion of the cases unexplained. In this work, the whole-exome sequencing approaches were used on 19 unrelated patients with unexplained colonic polyposis to identify candidate CRC predisposition genes. The candidate genes were then validated in an additional series of 365 patients. CRISPR-Cas9 models were used to validate BMPR2 as a potential candidate for CRC risk. 8 individuals carrying 6 different variants in the BMPR2 gene. CRISPR-Cas9 models of 3 of these variants showed that the p.(Asn442Thrfs∗32) truncating variant completely abrogated BMP pathway function in a similar way to the BMPR2 knockout.

Fig1. Quantitative analysis of the phosphorylated levels of SMAD1 (Ser463/465) by means of enzyme-linked immunosorbent assay in the presence or absence of 50 ng/mL of BMP4.

Fig2. MTS cell proliferation assay in the presence or absence of 50 ng/mL of BMP4.

Case Study 2: Arindam Mondal, 2021

Recent studies have shown that bone morphogenetic protein receptor 2 (BMPR2) regulates cell survival signaling events in cancer cells independent of the BMP type 1 receptor (BMPR1) or the Smad-1/5 transcription factor. Mutations in BMPR2 trafficking proteins leads to overactive BMP signaling, which leads to neurological diseases caused by BMPR2 stabilization of the microtubules. It is not known whether BMPR2 regulates the microtubules in cancer cells and what effect this has on cell survival. It is also not known whether alterations in BMPR2 trafficking effects activity and response to BMPR2 inhibitors. The researchers utilized BMPR2 siRNA and the BMP receptor inhibitors JL5 and Ym155, which decrease BMPR2 signaling and cause its mislocalization to the cytoplasm. Using the JL5 resistant MDA-MD-468 cell line and sensitive lung cancer cell lines, they examined the effects of BMPR2 inhibition on BMPR2 mislocalization to the cytoplasm, microtubule destabilization, lysosome activation and cell survival. Activated lysosomes further decreases BMPR2 signaling by causing it to mislocalizated to the cytoplasm and/or lysosome for degradation. Inhibition of the lysosomes with chloroquine attenuates BMPR2 trafficking to the lysosome and cell death induced by BMPR2 inhibitors.

Fig3. Immunoblot for BMPR2 of untreated cell lines.

Fig4. Western blot analysis for BMPR2 with JL5 combined with Ym155 with and without VAD and chloroquine.

Fig1. MP signaling in endothelial cells. (Mar Orriols, 2017)

Fig2. The BMP pathway in the colon. (Laia Bonjoch, 2023)

BMPR2 involved in several pathways and played different roles in them. We selected most pathways BMPR2 participated on our site, such as Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, Hippo signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with BMPR2 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

BMPR2 has several biochemical functions, for example, ATP binding, BMP binding, activin receptor activity, type II. Some of the functions are cooperated with other proteins, some of the functions could acted by BMPR2 itself. We selected most functions BMPR2 had, and list some proteins which have the same functions with BMPR2. You can find most of the proteins on our site.

BMPR2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with BMPR2 here. Most of them are supplied by our site. Hope this information will be useful for your research of BMPR2.

PRKG1; C4bpa; Prkcb; GDF5; MAPK8; Bmpr2; Ctbp1; Mos; Serpina3k; Lsp1; Cryab