GTP-dependent conformational changes associated with the functional switch between G α and cross-linking activities in brain-derived tissue transglutaminase 1 1Edited by P. E. Wright

Monsonego, Alon; Friedmann, Igor; Shani, Yael; Eisenstein, Miriam; Schwartz, Michal

doi:10.1006/jmbi.1998.2052

Cited by 42 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…45 Several in vitro studies describe in detail the inhibitory effect of GTP binding on tTG activity 23,46 and its interplay with other regulatory elements. 47 In addition, GTP binding causes conformational changes in tTG that affect both enzymatic activity 23,48,49 and interactions with other proteins including proteolytic enzymes. 23,28,50 Conformational changes able to modulate tTG activity are also described following binding of sphingosylphosphocholine.…”

Section: Discussionmentioning

confidence: 99%

Tissue transglutaminase is a caspase substrate during apoptosis. Cleavage causes loss of transamidating function and is a biochemical marker of caspase 3 activation

et al. 1999

View full text Add to dashboard Cite

Tissue transglutaminase (tTG) is a Ca 2+ -dependent crosslinking enzyme that participates in the apoptotic machinery by irreversibly assembling a protein scaffold that prevents the leakage of intracellular components. In the present study a single-chain antibody fragment (scFv) detecting tTG is described. We demonstrate that TG/F8 scFv, selected from a phase display library of human Vgene segments by binding to guinea-pig liver tTG, can react with human tTG both in Western blot and in immunohistochemistry. The specific detection of tTG by TG/F8 in human thymocytes is verified by mass spectrometric analysis of the purified protein. Furthermore, we demonstrate that in lymphoid cells tTG is cleaved by caspase 3 during the late phase of apoptotic death, concomitant to DNA fragmentation, and that such cleavage causes loss of cross-linking function. We propose tTG cleavage as a valuable biochemical marker of caspase 3 activation during the late execution phase of apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Tissue transglutaminase is a caspase substrate during apoptosis. Cleavage causes loss of transamidating function and is a biochemical marker of caspase 3 activation

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Yet, the nucleotide was found to stabilize the enzyme against heat denaturation (41) and against proteolytic degradation (15,17). In addition, the immunoreactivity of a C-terminal fragment (residues 666-680) of rat brain TGwhich, incidentally, includes a proposed PLC-binding site (8)-is markedly altered in the presence of GTP (42). This latter study would seem to suggest that the binding of GTP is accompanied by significant movements and rearrangements of the protein structure.…”

Section: Gtp-induced Changes In Transglutaminasementioning

confidence: 99%

Interactions of G _h /transglutaminase with phospholipase Cδ1 and with GTP

Murthy

Lomasney

Mak

et al. 1999

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

View full text Add to dashboard Cite

The inositol phosphate hydrolyzing activity of human phospholipase C␦1 (PLC␦1) is markedly inhibited when the enzyme is coexpressed with the human heart Gh͞transglutaminase (TG) in human embryonic kidney cells. Because the cotransfection does not affect the amount of PLC␦1 in the cells, the depression of phospholipase activity probably is a result of a direct interaction between the two proteins. An ELISA procedure was employed to document the associations of purified TG preparations from a variety of tissues (human red cells, rabbit lens, guinea pig liver) with PLC␦1. Nucleotides (GTP > GDP > ATP > GMP ‫؍‬ ADP, in order of decreasing efficiency) interfered with the formation of the PLC␦1:TG complex. A conformational change in the TG partner, occurring with nucleotide binding, is thought to be responsible for dissociating the two proteins. The structural rearrangement produces a remarkable shift in the anodic mobility of TG in electrophoresis: TGslow ؉ GTP u [TG:GTP]fast. Altogether, our findings indicate that GTP controls PLC␦1 activity by releasing this protein from an inhibitory association with G h͞transglutaminase.

show abstract

“…Importantly, MT1-MMP cleavage at any of these three sites should eliminate both the receptor and enzymatic activity of tTG by separating its NH 2 -terminal Fn binding and the COOH-terminal integrin binding domains (35,47) and by inactivating its second (catalytic) domain (Fig. 2, c and d).…”

mentioning

confidence: 99%

Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and Locomotion

Belkin

Akimov²,

Zaritskaya

et al. 2001

Journal of Biological Chemistry

224

206

View full text Add to dashboard Cite

Cell invasion requires cooperation between adhesion receptors and matrix metalloproteinases (MMPs). Remodeling of the extracellular matrix (ECM)1 is critical for cancer cell invasion and tumorigenesis (1-5). Membrane type matrix metalloproteinases (MT-MMPs) localized to the invasive front of highly motile cancer cells (6, 7) were shown to be directly involved in matrix breakdown (8 -13). A cooperation involving MT-MMPs and cell adhesion receptors is likely to be essential to migrating cells (3, 14 -16). So far, six members of the MT-MMP subfamily have been identified and partially characterized (2, 17-22). MT1-, MT2-, and MT3-MMP strongly contribute to tumor cell invasion (12). Recent studies demonstrated a functional significance and a direct role of MT1-, MT2-, and MT3-MMP in cell locomotion on laminin-5 (11) and three-dimensional collagen type I lattice (8, 9, 12). In addition, MT-MMPs contribute indirectly to cell invasion by activating soluble secretory MMP-2 (23) and MMP-13 (24), which further cleave multiple matrix substrates (2, 5, 25-29).Integrin adhesion receptors dynamically regulate cell-matrix interactions by the binding to matrix proteins and inside-out signaling (30,31). This allows cells to discriminate any subtle alteration of the environment and to adjust cell locomotion accordingly. Direct interactions with multiple transmembrane and cell surface proteins (32) including integrin-associated protein-50 (33), TM4SF proteins (tetraspanins) (34) and tTG (35) further attenuate adhesive and signaling efficiency of integrins.Cell surface tTG (protein-glutamine ␥-glutamyltransferase, EC 2.3.2.13) promotes integrin-dependent adhesion and spreading of cells. By both direct associations with multiple ␤ 1 and ␤ 3 integrins and the binding with Fn, tTG independently mediates the interactions of integrins with Fn (35). The high affinity binding of tTG with Fn specifically involves the 42 kDa gelatin-binding domain of the Fn molecule, which consists of modules I 6 II 1,2 I 7-9 (36). The enhancement of integrin-mediated adhesion and spreading of cells on Fn is independent from the enzymatic activity of surface tTG (35). Intriguingly, reduced expression of tTG has been linked to aggressiveness and high metastatic potential of tumors, whereas overexpression of tTG in fibrosarcomas inhibited primary tumor growth (37, 38). Proteolysis of tTG at the normal tissue/tumor boundary was observed in invasive tumors (38).Here, we report that depending on the structure of the ECM, MT-MMPs are capable of both positively and negatively regulating locomotion of cancer cells. Matrix-dependent proteolysis of surface tTG by MT1-MMP occurs on tumor cells of a diverse tissue origin, thereby representing a general phenomenon and a novel MT-MMP function. Our data suggest an existence of an unexpected link between tumor cell locomotion, the ECM and membrane-anchored MMPs. Regulatory proteolysis of cell surface adhesion proteins by the adjacent MT-MMP molecules is likely to play a significant functional role in cancer cell invasion.

show abstract

GTP-dependent conformational changes associated with the functional switch between G α and cross-linking activities in brain-derived tissue transglutaminase 1 1Edited by P. E. Wright

Cited by 42 publications

References 27 publications

Tissue transglutaminase is a caspase substrate during apoptosis. Cleavage causes loss of transamidating function and is a biochemical marker of caspase 3 activation

Tissue transglutaminase is a caspase substrate during apoptosis. Cleavage causes loss of transamidating function and is a biochemical marker of caspase 3 activation

Interactions of G _h /transglutaminase with phospholipase Cδ1 and with GTP

Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and Locomotion

Contact Info

Product

Resources

About

GTP-dependent conformational changes associated with the functional switch between G α and cross-linking activities in brain-derived tissue transglutaminase 1 1Edited by P. E. Wright

Cited by 42 publications

References 27 publications

Tissue transglutaminase is a caspase substrate during apoptosis. Cleavage causes loss of transamidating function and is a biochemical marker of caspase 3 activation

Tissue transglutaminase is a caspase substrate during apoptosis. Cleavage causes loss of transamidating function and is a biochemical marker of caspase 3 activation

Interactions of G h /transglutaminase with phospholipase Cδ1 and with GTP

Matrix-dependent Proteolysis of Surface Transglutaminase by Membrane-type Metalloproteinase Regulates Cancer Cell Adhesion and Locomotion

Contact Info

Product

Resources

About

Interactions of G _h /transglutaminase with phospholipase Cδ1 and with GTP