Details

Autor(en) / Beteiligte

• Nanda, N
• Iismaa, SE
• Owens, WA
• Husain, A
• Mackay, F
• Graham, R M

Titel

Targeted Inactivation of G sub(h)/Tissue Transglutaminase II

Ist Teil von

• The Journal of biological chemistry, 2001-06, Vol.276 (23), p.20673-20678

Erscheinungsjahr

2001

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The novel G-protein, G sub(h)/tissue transglutaminase (TGase II), has both guanosine triphosphatase and Ca super(2+)-activated transglutaminase activity and has been implicated in a number of processes including signal transduction, apoptosis, bone ossification, wound healing, and cell adhesion and spreading. To determine the role of G sub(h) in vivo, the Cre/loxP site-specific recombinase system was used to develop a mouse line in which its expression was ubiquitously inactivated. Despite the absence of G sub(h) expression and a lack of intracellular TGase activity that was not compensated by other TGases, the Tgm2 super(-/-) mice were viable, phenotypically normal, and were born with the expected Mendelian frequency. Absence of G sub(h) coupling to alpha sub(1)-adrenergic receptor signaling in Tgm2 super(-/-) mice was demonstrated by the lack of agonist-stimulated [ alpha - super(32)P]GTP photolabeling of a 74-kDa protein in liver membranes. Annexin-V positivity observed with dexamethasone-induced apoptosis was not different in Tgm2 super(-/-) thymocytes compared with Tgm2 super(+/+) thymocytes. However, with this treatment there was a highly significant decrease in the viability (propidium iodide negativity) of Tgm2 super(-/-) thymocytes. Primary fibroblasts isolated from Tgm2 super(-/-) mice also showed decreased adherence with culture. These results indicate that G sub(h) may be importantly involved in stabilizing apoptotic cells before clearance, and in responses such as wound healing that require fibroblast adhesion mediated by extracellular matrix cross- linking.