Growth factors stimulate kidney proximal tubule cell migration independent of augmented tyrosine phosphorylation of focal adhesion kinase

Cao, Yangming; Baig, Masood R.; Hamm, L. Lee; Wu, Kaidi; Simon, Eric E.

doi:10.1016/j.bbrc.2005.01.010

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…Based on our further observation that Herbimycin A did not abrogate Tyr397 phosphorylation of FAK it can be speculated that Tyr397 of FAK is a direct EFG target (Fig. 12, curl 1), as suggested by analogous studies on fibroblasts, which exhibited stimulation of Tyr397 phosphorylation in response to endothelin, an endothelium-derived peptide hormone consortium [55]. Further, previous studies on FAK-EGFR interaction have shown that the binding of the FAK-N-terminal region to the EGFR appears to be sufficient to induce strong EGF-mediated FAK phosphorylation at Tyr397 [23].…”

Section: Discussionmentioning

confidence: 81%

Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors

Eberwein

Laird

Schulz

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Within the concept of integrin growth factor receptor (GFR) cross-talk, little is known about the effects of GFRs on focal adhesions (FAs). Therefore, we tested the hypothesis whether EGF can modulate constituents of FAs and subsequent down-stream events. To this end, EGF-treated keratinocytes were subjected to combined fluorescence imaging and western blotting, to quantify expression and/or activation of molecules, involved in integrin GFR cross-talk, and receptor proximal and distal signaling events. Generally, EGF response revealed an amplified redistribution or activation of molecules under study, which will be explained in detail from the plasma membrane to the cell interior. In addition to significant activation of EGF receptor (EGFR) at tyrosine Tyr845, a remarkable redistribution was detectable for the focal adhesion constituents, integrin ß1 and ß3, and zyxin. Increased activation also applied to focal adhesion kinase (FAK) by phosphorylation at Tyr397, Tyr576, and Src at Tyr418, while total FAK remained unchanged. Risen activity was seen as well for the analyzed distal down-stream events, p190RhoGAP and MAP kinases p42/44. Intriguingly, Src-specific inhibitor Herbimycin A abrogated the entire EGF response except FAK Tyr397 phosphorylation, independent of EGF presence. Mechanistically, our results show that EGF modulates adhesion in a dual fashion, by firstly redistributing focal adhesion constituents to adhesion sites, but also by amplifying levels of activated RhoA antagonist p190RhoGAP, important for cell motility. Further, the findings suggest that the observed EGF response underlies an EGFR integrin cross-talk under recruitment of receptor proximal FAK and Src, and MAP kinase and p190RhoGAP as receptor distal events.

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Section: Discussionmentioning

confidence: 81%

Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors

Eberwein

Laird

Schulz

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…We have also been able to obtain phosphorylation profiles of these selected tyrosine kinases and serine/threonine kinases in the mTOR and PKC pathways from rhabdomyosarcoma patient tissues. These protein kinases have been shown to contribute to cell proliferation and cell survival [31][32][33][34][35][36][37][38][39][40][41][42] and most of them are likely to play crucial roles in tumor development and progression of rhabdomyosarcomas. Therefore, selective small molecular inhibitors that block these activated protein kinases may be useful therapeutic reagents.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation profiles of protein kinases in alveolar and embryonal rhabdomyosarcoma

et al. 2007

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Rhabdomyosarcoma is the most common pediatric soft-tissue sarcoma, which includes two major subtypes, alveolar and embryonal rhabdomyosarcoma. The mechanism of its oncogenesis is largely unknown. However, the oncogenic process of rhabdomyosarcoma involves multi-stages of signaling protein dysregulation characterized by prolonged activation of tyrosine and serine/threonine kinases. To better understand this protein dysregulation, we evaluated the phosphorylation profiles of multiple tyrosine and serine/threonine kinases to identify whether these protein kinases are activated in rhabdomyosarcoma. We applied immunohistochemistry with phospho-specific antibodies to examine phosphorylation levels of selected receptor and non-receptor tyrosine kinases, mammalian target of rapamycin (mTOR), p70S6K, and protein kinase C (PKC) isozymes on alveolar and embryonal rhabdomyosarcoma tissue microarray slides. Our results showed that the phosphorylation levels of these kinases are elevated in some rhabdomyosarcoma tissues compared to normal tissues. Phosphorylation levels of receptor and non-receptor tyrosine kinases are elevated between 26 and 68% in alveolar rhabdomyosarcoma and between 24 and 71% in embryonal rhabdomyosarcoma, respectively, compared to normal tissues. In addition, phosphorylation levels of mTOR and its downstream targets, p70S6K, S6, and 4EBP1, are increased between 50 and 72% in both subtypes of rhabdomyosarcoma. Further, phosphorylation levels of PKCa, PKCd, PKCh, and PKCf/k are upregulated between 57 and 69% in alveolar rhabdomyosarcoma and between 43 and 72% in embryonal rhabdomyosarcoma. This is the first report to create a phosphorylation profile of tyrosine and serine/threonine kinases involved in the mTOR and PKC pathways of alveolar and embryonal rhabdomyosarcoma. These protein kinases may play roles in the development or tumor progression of rhabdomyosarcomas and thus may serve as novel targets for therapeutic intervention. Most of these tumors arise in the head and neck region, genitourinary tract, and extremities. The two main histological subtypes of rhabdomyosarcoma are embryonal rhabdomyosarcoma, which comprises more than half of all rhabdomyosarcoma cases, and alveolar rhabdomyosarcoma, which is less common but more aggressive. These two subtypes arise at different primary body sites and have different age patterns.2 Clinically, the presentation of rhabdomyosarcoma is genetically heterogeneous. However, some genetic markers have been identified. Among them, approximately 75% of alveolar rhabdomyosarcoma are characterized by chromosomal translocation, most frequently, t(2;13)(q35;q14) or the variant t(1;13)(q36;q14). 3These translocations can disrupt either the PAX3

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“…EGF, HGF, and IGF-1 are known to stimulate recovery and cell migration in experimental acute renal failure [10] . Since current evidence supports the para-or autocrine role of growth factors in repair and regeneration of ischemic or nephrotoxic experimental acute renal failure, we evaluated the effects of different growth factors on human renal tubular cells of the early distal segment in vitro.…”

Section: Discussionmentioning

confidence: 99%

Different Effects of Growth Factors on Human Renal Early Distal Tubular Cells in vitro

Baer

Geiger²

2006

Kidney Blood Press Res

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Background: In the kidney, recovery from tubular damage requires regenerative mechanisms leading to re-epithelialization of the injured tubules. Current evidence supports the para- or autocrine role of growth factors in repair and regeneration of ischemic or nephrotoxic experimental acute renal failure. Methods: We evaluated the effects of EGF, HGF, IGF-1, and bFGF on human renal thick ascending limb and distal convoluted cells (TALDC) in vitro. TALDC were isolated by immunomagnetic separation and cultured. Signal transduction of the growth factors was evaluated by Western blot of ERK1/2 MAP-K phosphorylation. Cell proliferation was measured by MTT assay and a fluorometric assay. Results: A significant, dose- and time-dependent phosphorylation of ERK1/2 could be detected exclusively after stimulation with EGF. No other growth factor induced a significant MAPK phosphorylation. In the same manner, proliferation assays showed a significant growth-promoting effect of EGF. Neither HGF, nor IGF-1 or bFGF showed a stimulative effect on TALDC proliferation. Conclusion: The present study highlights the effects of growth factors on cultured TALDC and supports the hypothesis that in vivo EGF plays a para- or autocrine role during renal repair mechanisms.

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Growth factors stimulate kidney proximal tubule cell migration independent of augmented tyrosine phosphorylation of focal adhesion kinase

Cited by 9 publications

References 36 publications

Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors

Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors

Phosphorylation profiles of protein kinases in alveolar and embryonal rhabdomyosarcoma

Different Effects of Growth Factors on Human Renal Early Distal Tubular Cells in vitro

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