scholarly journals Primary Cilia and Coordination of Receptor Tyrosine Kinase (RTK) and Transforming Growth Factor β (TGF-β) Signaling

2016 ◽  
Vol 9 (6) ◽  
pp. a028167 ◽  
Author(s):  
Søren T. Christensen ◽  
Stine K. Morthorst ◽  
Johanne B. Mogensen ◽  
Lotte B. Pedersen
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Primary Cilia ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Proxy activation of protein ErbB2 by heterologous ligands implies a heterotetrameric mode of receptor tyrosine kinase interaction

1998 ◽  
Vol 331 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Guo Cai HUANG ◽  
Xiaomei OUYANG ◽  
Richard J. EPSTEIN
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Epidermal Growth Factor Receptors ◽  
Type I ◽  
A431 Cells ◽  
Erbb2 Receptor ◽  
Epidermal Growth

The oncoprotein ErbB2 is frequently overexpressed in human tumours, but no activating ErbB2-specific ligand has yet been identified. Here we analyse the catalytic and oligomeric behaviour of ErbB2 using phosphorylation-state-specific antibodies which distinguish kinase-active and -inactive ErbB2 receptor subsets. Heregulin-α (HRG) activates ErbB2 in G8/DHFR 3T3 cells by selectively inducing hetero-oligomerization with kinase-defective ErbB3, indicating that heterologous transphosphorylation is an unlikely prerequisite for ErbB2 activation. HRG also triggers association of epidermal-growth-factor receptors (EGFR) with a kinase-inactive ErbB2 subset while reducing EGFR association with active ErbB2. Similarly, EGF treatment of A431 cells induces concomitant hetero-oligomerization of active ErbB2 with inactive EGFR, of active EGFR with inactive ErbB2, and of inactive ErbB2 with kinase-defective ErbB3. These combinatorial patterns of ligand-dependent oligomerization suggest a multivalent model of receptor tyrosine kinase interaction in which liganded homodimers provide stable oligomerization interfaces for unliganded ErbB2 or other bystander receptors. We submit that ErbB2 may be physiologically activated via a ‘proxy ’ ligand-inducible heterotetrameric mechanism similar to that already established for transforming-growth-factor-β type I receptors.

scholarly journals Activation of phospholipase A2 and stimulation of prostaglandin E2 production by transforming growth factor-α in rat thymic epithelial cells requires influx of calcium

1993 ◽  
Vol 293 (1) ◽  
pp. 109-113 ◽  
Author(s):  
P Liu ◽  
M Wen ◽  
L Sun ◽  
J Hayashi
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Enzymic Activity ◽  
Pge2 Production ◽  
Thymic Epithelial Cells ◽  
Factor I ◽  
Stimulation Of

The stimulation of both phospholipase A2 (PLA2) enzymic activity and the production of prostaglandin E2 (PGE2) by transforming growth factor-alpha (TGF-alpha) and Ca2+ ionophore A23187 in TEA3A1 rat thymic epithelial cells were studied. TGF-alpha by itself at various concentrations (5-200 ng/ml) had no effect on the stimulation of PGE2 production. A23187 (1 microgram/ml) by itself stimulated PGE2 production on average by 18-fold over the control. When TGF-alpha (50 ng/ml) was added to the cells in the presence of A23187, a synergistic stimulation (on average 45-fold) of PGE2 production was observed. Synergistic stimulation was also observed at the level of arachidonic acid released from phospholipid pools, suggesting the activation of PLA2 enzymic activity. We have found that this synergistic activation of PLA2 enzymic activity and subsequent stimulation of PGE2 production required the activation of epidermal growth factor (EGF) receptor tyrosine kinase and Ca2+ influx. This was shown by the fact that genistein, an inhibitor of tyrosine kinase, blocks the synergistic stimulation by TGF-alpha and A23187 and by the fact that the stimulation of PGE2 production by TGF-alpha and A23187 is dependent on the culture-medium Ca2+ concentrations. The requirement for Ca2+ influx instead of intracellular mobilization of Ca2+ was shown by the fact that PGE2 production was not stimulated when cells were treated with TGF-alpha and thapsigargin. Moreover, the synergistic stimulation of PGE2 production by TGF-alpha and A23187 was not affected in protein kinase C down-modulated cells. In addition, the synergistic stimulation was not observed in cells treated with either phorbol 12-myristate 13-acetate (PMA) and TGF-alpha or PMA and A23187, and in cells treated with TGF-alpha and thapsigargin. The requirement for the activation of receptor tyrosine kinase seems to be specific to the EGF receptor, since a synergistic stimulation of PGE2 production was not observed when cells are treated with either insulin-like growth factor-I or fibroblast growth factor-I in the presence of A23187.

Perianale Fisteln bei CED: vom Mausmodell zur Klinik

2018 ◽  
Vol 75 (5) ◽  
pp. 287-294
Author(s):  
Michael Scharl
Keyword(s):  
Growth Factor ◽  
Morbus Crohn ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 13

Zusammenfassung. Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft dar.

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