Disease relevance of FZD5

• Together, these facts indicate that POU5F1 and POU2F subfamily members play a pivotal role for the FZD5 expression in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer [1].
• Both WNT5A and FZD5 also were detected in granulomatous lesions in the lungs of Mycobacterium tuberculosis-infected patients [2].
• Among human cancer cell lines, FZD5 was highly expressed in K-562 cells derived from chronic myelogenous leukemia [3].
• However, formylation of the N-terminal methionine of this hexapeptide restored its effect on adhesion and reduced tumor cell motility via a Frizzled-5 receptor-dependent mechanism, even at a low pH such as encountered in breast tumor tissue [4].
• Fzd5 membrane staining was detected in 30% of clear cell carcinomas, and there was a strong correlation with nuclear cyclin D1 staining in the samples [5].

High impact information on FZD5

• Wnt-5A induced axis duplication and an ectopic Spemann organizer in the presence of hFz5, a member of the Frizzled family of seven-transmembrane receptors [6].
• We show that human peripheral-blood mononuclear cells express the WNT5A receptor Frizzled-5 (FZD5) [2].
• Furthermore, among the three known Wnt pathways, Fz5/8 appears to signal via the planar cell polarity pathway [7].
• During development, Fz5/8 displays restricted expression, beginning at the 60-cell stage in the animal domain and then from mesenchyme blastula stage, in both the animal domain and a subset of secondary mesenchyme cells (SMCs) [7].
• GSK-3beta is a component of the wnt signaling pathway, and EC express wnt-5a and T cells express frizzled-5, a wnt-5a receptor [8].

Biological context of FZD5

• Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint) [1].
• Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites [1].
• FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology [1].
• We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5 [1].
• The 7.5- and 3.5-kb FZD5 mRNAs were transcribed probably due to alternative splicing [3].

Anatomical context of FZD5

• Functional studies showed that WNT5A and FZD5 regulate the microbially induced interleukin-12 response of antigen-presenting cells and interferon-gamma production by mycobacterial antigen-stimulated T cells [2].
• FZD5 was highly expressed in fetal liver and adult pancreas, and moderately expressed in fetal lung, kidney and adult liver [3].
• Previously, we found that these FLS expressed high levels of both Wnt-5A and Frizzled 5 (Fz5), a receptor-ligand pair implicated in both limb bud and bone marrow stem cell development [9].

Other interactions of FZD5

• Among human FZD family, FZD8 was most homologous to FZD5 (total amino-acid identity 69.1%) [10].
• For FZD5, we did not observe a segregating variant, however, for PTHR2, a missense variant (A225S) cosegregated with FOA in one family [11].
• Wnt-independent activation of beta-catenin mediated by a Dkk1-Fz5 fusion protein [12].

Analytical, diagnostic and therapeutic context of FZD5

• Western blot analysis of crude membrane fractions revealed that Fzd5 protein expression in the matched tumor/normal kidney samples correlated with the observed mRNA level [5].

References