Disease relevance of ADAM22

• ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain [1].
• Further analysis of ADAM22 will provide clues to understanding the mechanisms of human diseases such as epileptic seizures and peripheral neuropathy [2].

High impact information on ADAM22

• ADAM22 can act to inhibit cell proliferation, however, it has been suggested that it also acts as an adhesion protein [3].
• Deletion of both 14-3-3 binding sites and newly identified ER retention motifs restored localization of ADAM22 at the cell surface [3].
• ADAM22 point mutants lacking functional 14-3-3 protein binding motifs could no longer accumulate efficiently at the cell surface [3].
• In addition, we show that 14-3-3 proteins interact preferentially with the serine phosphorylated precursor form of ADAM22 [3].
• The interaction between ADAM22 and 14-3-3 proteins is dependent on phosphorylation of ADAM22, but not of 14-3-3 proteins [3].

Chemical compound and disease context of ADAM22

• The effects of overexpression of ADAM11 and ADAM22 in glioma cells on growth were analyzed using bromodeoxyuridine incorporation linked to immunocytochemistry [1].

Biological context of ADAM22

• Human chromosomal mapping indicated that ADAM22 and ADAM23 mapped to chromosome 7q21 and 2q33, respectively, while the three pseudogenes 1-2, 3-3, and 1-32 mapped to chromosome 14q24.1, 8p23, and 14q24.1, respectively [4].
• These results strongly demonstrated a functional role for ADAM22/14-3-3 in cell adhesion and spreading [5].
• Finally, the control of RNA degradation for the normalization of genes of interest was also tested. mRNA expression levels for superoxide dismutase 1 (SOD1) and metalloproteinase domain 22 (ADAM22) were examined at several artificial post-mortem times, and their expression levels compared with those for putative controls beta-actin and GUS [6].
• Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission [7].
• Using a classical mutagenesis and selection approach we have isolated a Nonomuraea sp. ATCC 39727 mutant strain able to direct production towards new A40926 analogues dechloro-A40926 (DDC) lacking two chlorine atoms and the two monochloro-A40926 (MDC1 and MDC2) that are not produced fermenting the wild type strain [8].

Anatomical context of ADAM22

• In vitro, ADAM22 inhibits cellular proliferation of glioma derived astrocytes [1].
• Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice [2].
• Human blood dendritic cells (BDC) can be divided into three subsets: plasmacytoid DC (PDC) and two myeloid subsets--MDC1 and MDC2 [9].

Associations of ADAM22 with chemical compounds

• CONCLUSION: ADAM22, a brain-specific cell surface protein, mediates growth inhibition using an integrin dependent pathway [1].
• Similarly analyzed were the effects on cell proliferation of bacterially expressed glutathione S-transferase fusion proteins with the disintegrin domain of ADAM11 and ADAM22 [1].

Other interactions of ADAM22

• These findings suggest that three murine cDNAs that we have isolated are the murine ADAM11, ADAM22 and ADAM23 cDNAs [10].

Analytical, diagnostic and therapeutic context of ADAM22

• In this paper, we report the cloning and sequence analysis of two novel additional members of this family, which we have termed MDC2 and MDC3 [11].
• We identified three 14-3-3 protein members by a yeast two-hybrid screen and show by co-immunoprecipitation that the cytoplasmic domain of ADAM22 can interact with all six 14-3-3 proteins expressed in the brain [3].
• METHODS: Specimens of low- and high-grade gliomas and normal brain were analyzed for ADAM11 and ADAM22 expression using Western blotting [1].
• To elucidate the physiological functions of ADAM22, we employed gene targeting to generate ADAM22 knockout mice [2].
• The three main subsets of BDC were distinguished by flow cytometry: BDCA-2(+)/CD123(+)/HLA-DR(+) (plasmacytoid, PDC) and two myeloid subtypes BDCA-1(+)/CD11c(+)/HLA-DR(+) (MDC1) and BDCA-3(+)/CD32(-)/HLA-DR(+) (MDC2) [12].

References