Activation of p21ras/MAPK Signal Transduction Molecules Decreases with Age in Mitogen-Stimulated T Cells from Rats

Pahlavani, Mohammad A.; Harris, Melissa D.; Richardson, Arlan

doi:10.1006/cimm.1998.1274

Cited by 47 publications

(29 citation statements)

References 72 publications

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“…Because T cell responses such as proliferation, differentiation, and gene expression are critically dependent on signal transduction cascades, several studies have been focused on the effect of age on the activation or the levels of signal transduction molecules (reviewed in 6). For example, our laboratory has recently shown that the induction of Ras and MAPK activity but not JNK activity by Con A decreased with age (33). In addition, we found that this decrease was paralleled by a decrease in the induction of TCR-associated protein tyrosine kinases, Lck (p56 lck ) and ZAP-70 activities, but not Fyn activity (33).…”

Section: Proliferation (Pha) ----------No Change Proliferation (Pwm) mentioning

confidence: 53%

“…For example, our laboratory has recently shown that the induction of Ras and MAPK activity but not JNK activity by Con A decreased with age (33). In addition, we found that this decrease was paralleled by a decrease in the induction of TCR-associated protein tyrosine kinases, Lck (p56 lck ) and ZAP-70 activities, but not Fyn activity (33). A recent study in human has confirmed our finding and showed that the induction of p56 lck and ZAP-70 activities decreased with age (34).…”

Section: Proliferation (Pha) ----------No Change Proliferation (Pwm) mentioning

confidence: 99%

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Caloric restriction and immunosenescence: a current perspective

Pahlavani

2000

Front Biosci

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Section: Proliferation (Pha) ----------No Change Proliferation (Pwm) mentioning

confidence: 53%

Section: Proliferation (Pha) ----------No Change Proliferation (Pwm) mentioning

confidence: 99%

Caloric restriction and immunosenescence: a current perspective

Pahlavani

2000

Front Biosci

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“…4), we examined the coupling of the EGF receptor to the ERK-MAP kinase signaling pathway. Age-related differences in the membrane complexes involved in signaling have previously been reported in T-lymphocytes (35,39,40) and B-cells (41). We have identified an early step in the EGF receptor signal transduction pathway to be a decrease in the association of the adapter protein, Shc, with the activated EGF receptor in hepatocytes from old compared with young (Fig.…”

Section: Discussionmentioning

confidence: 75%

Age-dependent Decline in Mitogenic Stimulation of Hepatocytes

Palmer

Tuzon

Paulson

1999

Journal of Biological Chemistry

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The proliferative potential of the liver has been well documented to decline with age. However, the molecular mechanism of this phenomenon is not well understood. Cellular proliferation is the result of growth factor-receptor binding and activation of cellular signaling pathways to regulate specific gene transcription. To determine the mechanism of the age-related difference in proliferation, we evaluated extracellular signal-regulated kinase-mitogen-activated protein kinase activation and events upstream in the signaling pathway in epidermal growth factor (EGF)-stimulated hepatocytes isolated from young and old rats. We confirm the ageassociated decrease in extracellular signal-regulated kinase-mitogen-activated protein kinase activation in response to EGF that has been previously reported. We also find that the activity of the upstream kinase, Raf kinase, is decreased in hepatocytes from old compared with young rats. An early age-related difference in the EGF-stimulated pathway is shown to be the decreased ability of the adapter protein, Shc, to associate with the EGF receptor through the Shc phosphotyrosine binding domain. To address the mechanism of decreased Shc/ EGF receptor interaction, we examined the phosphorylation of the EGF receptor at tyrosine 1173, a site recognized by the Shc phosphotyrosine binding domain. Tyrosine 1173 of the EGF receptor is underphosphorylated in the hepatocytes from old animals compared with young in a Western blot analysis using a phosphospecific antibody that recognizes phosphotyrosine 1173 of the EGF receptor. These data suggest that a molecular mechanism underlying the age-associated decrease in hepatocyte proliferation involves an age-dependent regulation of site-specific tyrosine residue phosphorylation on the EGF receptor.

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“…Lectin-induced signaling had so far not been studied in intestinal epithelial cells. However, PHA-induced IL-2 production and secretion in human T-lymphocytes are mediated via the ERK pathway [31]and an activation of the p21ras/MAPK signal transduction cascade has recently been demonstrated in concanavalin A-stimulated lymphocytes [32]. In addition, PHA-induced production of lymphotoxin has been shown to activate the p21ras-raf-MEK-ERK cascade in Jurkat leukemic cells [33].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Lectin (Phytohemagglutinin)-Induced Growth in Small Intestinal Epithelial Cells

Otte¹,

Chen²,

Brunke³

et al. 2001

Digestion

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Background/Aims: The lectin phytohemagglutinin is a mitogen for intestinal epithelial cells in vivo. The mechanisms of action are unknown and were therefore analyzed in vitro. Methods: Human (Intestine-407) and rat (IEC-6; IEC-18) intestinal epithelial cell lines were stimulated with phytohemagglutinin. Proliferation was assayed by ³H-thymidine incorporation, activation of mitogen-activated protein kinase (MAPK) by Western blotting, and induction of c-fos mRNA expression by semiquantitative polymerase chain reaction. Control experiments were performed with phenyl-N-acetyl-α-D-galactosaminide or the tyrosine kinase inhibitor tyrphostin A25. Results: Phytohemagglutinin (0.1 µg/ml) significantly stimulated proliferation in all three cell lines after 48–72 h. MAPK activation was detected after 15–30 min, and an induction of c-fos mRNA expression after 15– 30 min of stimulation. Mitogenic effects were blocked by preincubation with phenyl-N-acetyl-α-D-galactosaminide or tyrphostin A25. Conclusion: Phytohemagglutinin stimulated proliferation, MAPK activation and induction of c-fos mRNA expression. The lectin may contribute to intestinal mucosal growth and regeneration thereby preventing gut atrophy.

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Activation of p21ras/MAPK Signal Transduction Molecules Decreases with Age in Mitogen-Stimulated T Cells from Rats

Cited by 47 publications

References 72 publications

Caloric restriction and immunosenescence: a current perspective

Caloric restriction and immunosenescence: a current perspective

Age-dependent Decline in Mitogenic Stimulation of Hepatocytes

Mechanisms of Lectin (Phytohemagglutinin)-Induced Growth in Small Intestinal Epithelial Cells

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