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Expression of protooncogenes during lymphocyte activation by growth factors
E G Bulanova1, V M Budagyan, A A Yarilin
1Institute of Immunology, Russian Ministry of Health Care, Moscow, Russia.
Abstract:
Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.
Insights
Non-immune growth factors like somatotropin (ST) and platelet-derived growth factor (PDGF) influence early T-lymphocyte activation by altering oncoprotein expression. These factors modulate Fos, Myc, and Jun protein dynamics, suggesting distinct roles in cell signaling pathways.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Growth factors of non-immune origin, such as somatotropin (ST) and platelet-derived growth factor (PDGF), play crucial roles in cellular processes.
- Protooncogenes encode proteins that regulate cell growth and differentiation, and their aberrant expression is linked to cancer.
- Lymphocyte activation is a complex process involving intricate signaling cascades.
Purpose of the Study:
- To investigate the effects of ST and PDGF on the expression of c-fos, c-myc, c-jun, and c-ets family protooncogenes in activated CD(3+)-lymphocytes.
- To elucidate the dynamics of oncoprotein accumulation during early lymphocyte activation.
- To understand the differential roles of c-ets-1 and c-ets-2 gene products in resting versus activated lymphocytes.
Main Methods:
- Immunoblotting was used to quantify the expression of specific oncoproteins (Fos, Myc, Jun, Ets-1, Ets-2).
- T-lymphocytes were activated using phytohemagglutinin in conjunction with ST or PDGF.
- Time-course analysis was performed to observe the dynamics of protein accumulation.
Main Results:
- Fos and Myc protein accumulation increased significantly in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin, peaking at 30-60 minutes.
- Jun protein expression was detected later, around 3 hours post-activation, suggesting Fos acts independently in early stages.
- Ets-1 protein was abundant in resting lymphocytes but decreased upon ST or PDGF activation, while Ets-2 was induced by ST but not PDGF.
- Ets-1 appears crucial for resting cells, whereas Ets-2 is important during ST-mediated lymphocyte activation.
Conclusions:
- Growth factors of non-immune origin modulate early lymphocyte activation through distinct signal transduction pathways.
- The differential expression of Fos, Myc, Jun, and Ets family proteins highlights their specific roles in T-lymphocyte activation dynamics.
- These findings provide novel insights into the molecular mechanisms underlying non-immune growth factor-mediated lymphocyte responses.