Mutational analysis of the FXNPXY motif within LDL receptor-related protein 1 (LRP1) reveals the functional importance of the tyrosine residues in cell growth regulation and signal transduction

2007 ◽  
Vol 409 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Hongyu Zhang ◽  
Jonathan M. Lee ◽  
Yuwei Wang ◽  
Li Dong ◽  
Kerry W. S. Ko ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Growth ◽  
Cellular Localization ◽  
Growth Regulation ◽  
Chinese Hamster Ovary Cells ◽  
Adaptor Protein ◽  
The Other ◽  
Related Protein ◽  
Cell Growth Regulation ◽  
Tumour Development

LRP1 [LDL (low-density lipoprotein) receptor-related protein 1]-null CHO cells (Chinese-hamster ovary cells) (13-5-1 cells) exhibited accelerated cell growth and severe tumour progression after they were xenografted into nude mice. Reconstitution of LRP1 expression in these cells, either with the full-length protein or with a minireceptor, reduced growth rate as well as suppressed tumour development. We tested the role of the tyrosine residue in the FXNPXY63 motif within the LRP1 cytoplasmic domain in signal transduction and cell growth inhibition by site-specific mutagenesis. The LRP1 minireceptors harbouring Tyr63 to alanine or Tyr63 to phenylalanine substitution had diametrically opposite effects on cell growth, cell morphology and tumour development in mice. The Y63F-expressing cells showed suppressed cell growth and tumour development, which were associated with decreased β-catenin and cadherin concentrations in the cells. On the other hand, the Y63A-expressing cells lacked inhibition on cell growth and tumour development, which were associated with hyperactivation of ERKs (extracellular-signal-regulated kinases), FAK (focal adhesion kinase) and cyclin D1 in the cells. The mutant Y63A minireceptor also exhibited reduced capacity in binding to the Dab2 (disabled 2) adaptor protein. In addition, the Y63A mutant showed increased caveolar localization, and cells expressing Y63A had altered caveolae architecture. However, tyrosine to alanine substitution at the other NPXY29 motif had no effect on cell growth or tumorigenesis. These results suggest that the FXNPXY63 motif of LRP1 not only governs cellular localization of the receptor but also exerts multiple functional effects on signalling pathways involved in cell growth regulation.

Dissecting the TOR?S6K signal transduction pathway in maize seedlings: relevance on cell growth regulation

2007 ◽  
Vol 130 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Tzvetanka D. Dinkova ◽  
Homero Reyes de la Cruz ◽  
Cristina García-Flores ◽  
Raul Aguilar ◽  
Luis Felipe Jiménez-García ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Growth ◽  
Growth Regulation ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Maize Seedlings ◽  
Cell Growth Regulation

MiR8181 is involved in the cell growth regulation of Saccharina japonica

2021 ◽  
pp. 153394
Author(s):  
Xiaoqi Yang ◽  
Xiuliang Wang ◽  
Jianting Yao ◽  
Wei Li ◽  
Delin Duan
Keyword(s):  
Cell Growth ◽  
Growth Regulation ◽  
Saccharina Japonica ◽  
Cell Growth Regulation

The ERK pathway involves positive and negative regulations of HT-29 colorectal cancer cell growth by extracellular zinc

2003 ◽  
Vol 285 (6) ◽  
pp. G1181-G1188 ◽  
Author(s):  
Ki-Sook Park ◽  
Nam-Gu Lee ◽  
Ki-Hoo Lee ◽  
Jeong Taeg Seo ◽  
Kang-Yell Choi
Keyword(s):  
Colorectal Cancer ◽  
Signal Transduction ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Growth Regulation ◽  
Erk Pathway ◽  
Differential Growth ◽  
Erk Activation ◽  
Ht 29

Dietary zinc is an important trace element in the body and is related to both cell proliferation and growth arrest. A recent study found that extracellular zinc-sensing receptors trigger intracellular signal transduction in HT-29 human colorectal cancer cells. However, the signaling mechanism causing this growth regulation by extracellular zinc is not clearly understood. At 10- and 100-μM levels of ZnCl2 treatment, HT-29 cell growth and proliferation increased and decreased, respectively, in a minimally serum-starved medium (MSSM). A lack of significant increase in intracellular zinc levels after zinc treatment suggested that this differential growth regulation of HT-29 cells by extracellular zinc is acquired by receptor-mediated signal transduction. Moreover, this zinc-induced growth regulation was differentially affected by PD-98059, suggesting the involvement of the ERK pathway. Transient ERK activation and subsequent cyclin D1 induction were observed on adding 10 μM ZnCl2 in MSSM in the presence of cell proliferation. On the other hand, prolonged ERK activity was observed with a subsequent increase of cyclin D1 and p21Cip/WAF1 on adding 100 μM ZnCl2 in MSSM, and this was associated with nonproliferation. Moreover, this ERK activation and cyclin D1 and p21Cip/WAF1 induction were abolished by PD-98059 pretreatment. The differential regulations of cell growth, ERK activities, and cyclin D1 and p21Cip/WAF1 inductions were also observed in serum-enriched medium containing higher zinc concentrations. Therefore, differential cell cycle regulator induction occurs by a common ERK pathway in the differential growth regulation of HT-29 cells by extracellular zinc.

Sphingolipid metabolism and cell growth regulation

1996 ◽  
Vol 10 (12) ◽  
pp. 1388-1397 ◽  
Author(s):  
Sarah Spiegel ◽  
Alfred H. Merrill
Keyword(s):  
Cell Growth ◽  
Growth Regulation ◽  
Sphingolipid Metabolism ◽  
Cell Growth Regulation

scholarly journals Signal Transduction in Human Hematopoietic Cells by Vascular Endothelial Growth Factor Related Protein, a Novel Ligand for the FLT4 Receptor

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3507-3515 ◽  
Author(s):  
Jian-Feng Wang ◽  
Ramesh K. Ganju ◽  
Zhong-Ying Liu ◽  
Hava Avraham ◽  
Shalom Avraham ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein A ◽  
Hematopoietic Cells ◽  
Adaptor Protein ◽  
Vascular Endothelial ◽  
Related Protein ◽  
Jnk Pathway ◽  
Endothelial Growth Factor

Abstract We have recently identified a novel ligand of the vascular endothelial growth factor (VEGF) family termed VEGF-related protein (VRP), which specifically binds to the FLT4 receptor. To characterize the signaling events after VRP engagement of its cognate receptor in hematopoietic cells, a population of human erythroleukemia (HEL) cells, termed HEL-JW, expressing high levels of FLT4 receptor was isolated. Stimulation of HEL-JW cells with VRP alone and in combination with the c-kit ligand/stem cell factor increased cell growth. VRP induced tyrosine phosphorylation of various proteins, including the FLT4 receptor. Further characterization of these tyrosine phosphorylated molecules revealed that Shc, Grb2, and SOS form a complex with the activated FLT4 receptor. HEL-JW cells also expressed RAFTK, a recently identified member of the focal adhesion kinase family. RAFTK was phosphorylated and activated upon VRP treatment, and there was an enhanced association of this kinase with the adaptor protein Grb2. Furthermore, the c-Jun NH2-terminal kinase (JNK), involved in growth activation and shown to mediate RAFTK signaling in other cell types, was activated by VRP stimulation. We also observed that VRP treatment of HEL-JW cells resulted in the phosphorylation of the cytoskeletal protein paxillin. This treatment resulted in an increased association of paxillin with RAFTK, which was mediated by the C-terminal region of RAFTK. These studies indicate that VRP stimulation induced the formation of a signaling complex at its activated receptor as well as activation of RAFTK. VRP-mediated activation of RAFTK may facilitate signal transduction to the cytoskeleton and downstream to the JNK pathway in FLT4-expressing blood cells.

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