Characterization of the adenosine deaminase-related growth factor (ADGF) gene family in Drosophila

Maier, Stefan A.; Podemski, Lynn; Graham, Sean W.; McDermid, Heather E.; Locke, John

doi:10.1016/s0378-1119(01)00762-4

Cited by 32 publications

(21 citation statements)

References 22 publications

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“…By searching databases for sequences encoding proteins related to the insect-derived growth factor from Sarcophaga cells (10), we identified six Drosophila genes encoding a family of ADGFs. The genomic organization of these genes is shown at our web site, http:͞͞mamba.bio.uci.edu͞ϳpjbryant͞lab͞ ADGFs͞index.htm, and has been independently described (11). The genes include one triplet in tandem at 3L;74E2, encoding ADGF-A and ADGF-B, as well as ADGF-A2, previously reported as male-specific insect-derived growth factor, or MSI (12).…”

Section: Resultsmentioning

confidence: 99%

Adenosine deaminase-related growth factors stimulate cell proliferation in Drosophila by depleting extracellular adenosine

Z̆urovec

Doležal

Gaži

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

105

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We describe a protein family in Drosophila containing six adenosine deaminase-related growth factors (ADGFs), which are homologous to a mitogenic growth factor discovered in conditioned medium from cells of a different fly species, Sarcophaga. Closely related proteins have been identified in other animals, and a human homolog is implicated in the genetic disease Cat-Eye Syndrome. The two most abundantly expressed ADGFs in Drosophila larvae are ADGF-A, which is strongly expressed in the gut and lymph glands, and ADGF-D, which is mainly expressed in the fat body and brain. Recombinant ADGF-A and ADGF-D are active adenosine deaminases (ADAs), and they cause polarization and serum-independent proliferation of imaginal disk and embryonic cells in vitro. The enzymatic activity of these proteins is required for their mitogenic function, making them unique among growth factors. A culture medium prepared without adenosine, or depleted of adenosine by using bovine ADA, also stimulates proliferation of imaginal disk cells, and addition of adenosine to this medium inhibits proliferation. Thus ADGFs secreted in vivo may control tissue growth by modulating the level of extracellular adenosine.

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Section: Resultsmentioning

confidence: 99%

Adenosine deaminase-related growth factors stimulate cell proliferation in Drosophila by depleting extracellular adenosine

Z̆urovec

Doležal

Gaži

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

105

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“…Several proteins of this subfamily have been shown to posses adenosine deaminase enzymatic activity Zurovec et al, 2001) and to be mitogenic in vitro (Homma et al, 1996;Zurovec et al, 2001). They have been found in flesh fly Sarcophaga peregrina (Homma et al, 1996), sand fly Lutzomyia longipalpis (Charlab et al, 2000), Drosophila (Maier et al, 2001), the sea hare mollusk Aplysia californica (Sossin et al, 1989;Akalal and Nagle, 2001) and human (Riazi et al, 2000). A homologous EST was detected in the slime mold Dictyostelium discoideum (Maier et al, 2001).…”

Section: Article In Pressmentioning

confidence: 99%

The emerging role of adenosine deaminases in insects

Doleželová

Z̆urovec

Doležal

et al. 2005

Insect Biochemistry and Molecular Biology

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“…The ADGF/ADA2 family proteins (3,14,15) were first described as growth factors in insects (16,17) and later were found to possess the ADA activity, which was shown to be essential for the growth factor activity (3,18,19). The physiological role is best described for the Drosophila homologue, ADGF-A (3,20).…”

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confidence: 99%

“…ADGF/ADA2 proteins contain considerably longer sequences than those of ADA1 proteins. One of the characteristic features of ADGF/ADA2 is an 80 -100-amino acid extension at the N terminus that was suggested to be responsible for their growth factor activity (3,14,15).…”

mentioning

confidence: 99%

Structural Basis for the Growth Factor Activity of Human Adenosine Deaminase ADA2

Zavialov

Spillmann

et al. 2010

Journal of Biological Chemistry

112

124

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Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp contrast with that of monomeric single domain ADA1. An extensive glycosylation and the presence of a conserved disulfide bond and a signal peptide in ADA2 strongly suggest that ADA2, in contrast to ADA1, is specifically designed to act in the extracellular environment. The comparison of catalytic sites of ADA2 and ADA1 demonstrates large differences in the arrangement of the substratebinding pockets. These structural differences explain the substrate and inhibitor specificity of adenosine deaminases and provide the basis for a rational design of ADA2-targeting drugs to modulate the immune system responses in pathophysiological conditions.

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Characterization of the adenosine deaminase-related growth factor (ADGF) gene family in Drosophila

Cited by 32 publications

References 22 publications

Adenosine deaminase-related growth factors stimulate cell proliferation in Drosophila by depleting extracellular adenosine

Adenosine deaminase-related growth factors stimulate cell proliferation in Drosophila by depleting extracellular adenosine

The emerging role of adenosine deaminases in insects

Structural Basis for the Growth Factor Activity of Human Adenosine Deaminase ADA2

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