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Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes.
J Immunol. 1997 Nov 01; 159(9):4155-64.JI

Abstract

The cell cycle events accompanying TGF-beta1-induced growth arrest of normal mouse resting B lymphocytes stimulated by LPS were investigated. We showed that TGF-beta1 prevents the retinoblastoma protein (pRb) phosphorylation and induces growth arrest in mid- to late G1. To explore the molecular basis of the effect of TGF-beta1, we analyzed the in vitro kinase activities of cyclin/cyclin-dependent kinase (cdk) complexes involved in the progression through G1 phase and in the G1/S transition, by using the glutathione S-transferase-pRb fusion protein as a substrate. Cdk2-associated kinase activity was strongly induced in mitogen-treated B cells. It was dramatically inhibited by TGF-beta1 as were the cyclin E- and cyclin A-dependent kinase activities. TGF-beta1 treatment had no significant effect on the expression of two G1/S phase proteins, cyclin E and cdk2. In contrast, the appearance of cyclin A, occuring in late G1 phase, was almost totally inhibited by TGF-beta1. We also showed that expression of the cdk inhibitor protein p27Kip1 decreased as cells progressed through the G1 phase. An accumulation of p27 was found in TGF-beta1-treated cells, showing that TGF-beta1 prevented LPS-induced decline of p27. Finally we found that the lack of kinase activity associated with cyclin E/cdk2 complexes was correlated with increased amounts of cdk2- and cyclin E-bound p27. Overall, these results suggest that both cyclin A and cdk2 may be active participants in the TGF-beta1-induced cell cycle arrest in normal mouse B cells and indicate the involvement of p27 in this mechanism.

Authors+Show Affiliations

Laboratoire d'Immunologie Cellulaire et Clinique, INSERM U255, Institut Curie, Paris, France.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9379008

Citation

Bouchard, C, et al. "Effect of TGF-beta1 On Cell Cycle Regulatory Proteins in LPS-stimulated Normal Mouse B Lymphocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 159, no. 9, 1997, pp. 4155-64.
Bouchard C, Fridman WH, Sautès C. Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes. J Immunol. 1997;159(9):4155-64.
Bouchard, C., Fridman, W. H., & Sautès, C. (1997). Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes. Journal of Immunology (Baltimore, Md. : 1950), 159(9), 4155-64.
Bouchard C, Fridman WH, Sautès C. Effect of TGF-beta1 On Cell Cycle Regulatory Proteins in LPS-stimulated Normal Mouse B Lymphocytes. J Immunol. 1997 Nov 1;159(9):4155-64. PubMed PMID: 9379008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes. AU - Bouchard,C, AU - Fridman,W H, AU - Sautès,C, PY - 1997/10/31/pubmed PY - 1997/10/31/medline PY - 1997/10/31/entrez SP - 4155 EP - 64 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 159 IS - 9 N2 - The cell cycle events accompanying TGF-beta1-induced growth arrest of normal mouse resting B lymphocytes stimulated by LPS were investigated. We showed that TGF-beta1 prevents the retinoblastoma protein (pRb) phosphorylation and induces growth arrest in mid- to late G1. To explore the molecular basis of the effect of TGF-beta1, we analyzed the in vitro kinase activities of cyclin/cyclin-dependent kinase (cdk) complexes involved in the progression through G1 phase and in the G1/S transition, by using the glutathione S-transferase-pRb fusion protein as a substrate. Cdk2-associated kinase activity was strongly induced in mitogen-treated B cells. It was dramatically inhibited by TGF-beta1 as were the cyclin E- and cyclin A-dependent kinase activities. TGF-beta1 treatment had no significant effect on the expression of two G1/S phase proteins, cyclin E and cdk2. In contrast, the appearance of cyclin A, occuring in late G1 phase, was almost totally inhibited by TGF-beta1. We also showed that expression of the cdk inhibitor protein p27Kip1 decreased as cells progressed through the G1 phase. An accumulation of p27 was found in TGF-beta1-treated cells, showing that TGF-beta1 prevented LPS-induced decline of p27. Finally we found that the lack of kinase activity associated with cyclin E/cdk2 complexes was correlated with increased amounts of cdk2- and cyclin E-bound p27. Overall, these results suggest that both cyclin A and cdk2 may be active participants in the TGF-beta1-induced cell cycle arrest in normal mouse B cells and indicate the involvement of p27 in this mechanism. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9379008/Effect_of_TGF_beta1_on_cell_cycle_regulatory_proteins_in_LPS_stimulated_normal_mouse_B_lymphocytes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=9379008 DB - PRIME DP - Unbound Medicine ER -