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T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation.

Authors: Acuna-Castillo, C  Aravena, M  Leiva-Salcedo, E  Perez, V  Gomez, C  Sabaj, V  Nishimura, S  Perez, C  Colombo, A  Walter, R  Sierra, F 
Citation: Acuna-Castillo C, etal., Mech Ageing Dev. 2005 Dec;126(12):1284-91. Epub 2005 Sep 2.
Pubmed: (View Article at PubMed) PMID:16140359
DOI: Full-text: DOI:10.1016/j.mad.2005.07.005

Plasma levels of kininogens increase with age in both rats and humans. Kininogens are inhibitors of cysteine proteinases, and filarial cysteine proteinase inhibitors (cystatins) reduce the proliferation of T cells. We evaluated whether T-kininogen (T-KG) might mimic this effect, and here we present data indicating that exposure of either rat splenocytes or Jurkat cells to purified T-KG results in inhibition of both ERK activation and [(3)H]-thymidine incorporation, both basal and in response to ConA or PHA. Interestingly, T-KG did not impair [(3)H]-thymidine incorporation in response to IL-2, which requires primarily the activation of the JNK and Jak/STAT pathways. These effects were neither the consequence of increased cell death, nor required the activity of kinin receptors. Furthermore, when T cell receptor proximal events were bypassed by the use of PMA plus Calcium ionophore, T-KG no longer inhibited ERK activation, suggesting that inhibition occurs upstream of these events, possibly at the level of membrane associated signal transduction molecules. We conclude that, like filarial cystatins, T-KG inhibits ERK-dependent T cell proliferation, and these observations suggest a possible role for T-KG in immunosenescence.

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CRRD Object Information
CRRD ID: 1600541
Created: 2007-03-13
Species: All species
Last Modified: 2007-03-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.