Chitinase 3-like protein 2 (CHI3L2, YKL-39) activates phosphorylation of extracellular signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells

Areshkov, P. O.; Kavsan, V. M.

doi:10.3103/s0095452710010019

Cited by 22 publications

(21 citation statements)

References 22 publications

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“…3A). These cells, similarly to 293 cells, but in contrast to other glioblastoma cell line U87 16 produce neither CHI3L1 nor CHI3L2 protein (Fig. 3B).…”

Section: Resultsmentioning

confidence: 71%

Two Closely Related Human Members of Chitinase-like Family, CHI3L1 and CHI3L2, Activate ERK1/2 in 293 and U373 Cells but Have the Different Influence on Cell Proliferation

Areshkov¹,

Avdieiev²,

Balynska³

et al. 2012

Int. J. Biol. Sci.

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The activation of extracellular signal-regulated kinases (ERK1/2) has been associated with specific outcomes. Sustained activation of ERK1/2 by nerve growth factor (NGF) is associated with translocation of ERKs to the nucleus of PC12 cells and precedes their differentiation into sympathetic-like neurons whereas transient activation by epidermal growth factor (EGF) leads to cell proliferation. It was demonstrated that different growth factors initiating the same cellular signaling pathways may lead to the different cell destiny, either to proliferation or to the inhibition of mitogenesis and apoptosis. Thus, further investigation on kinetic differences in activation of certain signal cascades in different cell types by biologically different agents are necessary for understanding the mechanisms as to how cells make a choice between proliferation and differentiation.It was reported that chitinase 3-like 1 (CHI3L1) protein promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts similarly to insulin-like growth factor 1 (IGF1). Both are involved in mediating the mitogenic response through the signal-regulated kinases ERK1/2. In addition, CHI3L1 which is highly expressed in different tumors including glioblastomas possesses oncogenic properties. As we found earlier, chitinase 3-like 2 (CHI3L2) most closely related to human CHI3L1 also showed increased expression in glial tumors at both the RNA and protein levels and stimulated the activation of the MAPK pathway through phosphorylation of ERK1/2 in 293 and U87 MG cells. The work described here demonstrates the influence of CHI3L2 and CHI3L1 on the duration of MAPK cellular signaling and phosphorylated ERK1/2 translocation to the nucleus. In contrast to the activation of ERK1/2 phosphorylation by CHI3L1 that leads to a proliferative signal (similar to the EGF effect in PC12 cells), activation of ERK1/2 phosphorylation by CHI3L2 (similar to NGF) inhibits cell mitogenesis and proliferation.

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“…3A). These cells, similarly to 293 cells, but in contrast to other glioblastoma cell line U87 16 produce neither CHI3L1 nor CHI3L2 protein (Fig. 3B).…”

Section: Resultsmentioning

confidence: 71%

Two Closely Related Human Members of Chitinase-like Family, CHI3L1 and CHI3L2, Activate ERK1/2 in 293 and U373 Cells but Have the Different Influence on Cell Proliferation

Areshkov¹,

Avdieiev²,

Balynska³

et al. 2012

Int. J. Biol. Sci.

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“…Enzymatically silent Glyco_18 domain-containing chitinase-like proteins do not bind chitin, but rather act as soluble mediators and might be involved in tumor progression [65,66,67,68,69,70] and disorders characterized by chronic inflammation and ECM remodeling, such as rheumatoid arthritis [71], inflammatory bowel disease [72], hepatic fibrosis and cirrhosis [73,74], and systemic sclerosis [75]. Crucial biological functions were assigned to mammalian chitinase-like proteins including mediation of cell differentiation, proliferation activation, migration, and adhesion [76,77,78,79,80,81], however, no receptors for chitinase-like proteins have been found until our identification of stabilin-1/SI-CLP as a ligand-receptor pair [57].…”

Section: Intracellular Sorting Function Of Stabilin-1: Transport To Tmentioning

confidence: 99%

Multifunctional Receptor Stabilin-1 in Homeostasis and Disease

Kzhyshkowska

2010

The Scientific World JOURNAL

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The multifunctional scavenger receptor stabilin-1 (STAB1, FEEL-1, CLEVER-1, KIAA0246) is expressed on tissue macrophages and sinusoidal endothelial cells in healthy organisms, and its expression on both macrophages and different subtypes of endothelial cells is induced during chronic inflammation and tumor progression. Stabilin-1 is a type-1 transmembrane receptor that mediates endocytic and phagocytic clearance of “unwanted-self” components, intracellular sorting of the endogenously synthesized chitinase-like protein SI-CLP, and transcytosis of the growth hormone family member placental lactogen. The central sorting station for stabilin-1 trafficking seems to be the trans-Golgi network (TGN). Transport of stabilin-1 in the TGN requires interaction with GGA adaptors that bind to the classical DDSLL motif and a novel acidic cluster in its cytoplasmic tail. Degradation of stabilin-1 seems to depend on the interaction with sorting nexin 17. However, the mechanisms keeping stabilin-1 on the cell surface remain to be identified. This issue deserves specific attention due to the growing amount of data indicating that function of stabilin-1 in cell adhesion events is essential for inflammation and metastasis. Taking into consideration the complexity of stabilin-1—mediated processes, investigation of stabilin-1 functions in the animal models, as well as mathematic modeling of intracellular trafficking and extracellular contact, would enable prediction of stabilin-1 behavior in complex biological systems and would open perspectives for therapeutic targeting of stabilin-1 pathways in chronic inflammation and carcinogenesis.

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“…YKL-39 was also found to induce an autoimmune response in patients with rheumatoid arthritis (22,23), as well as in a rheumatoid arthritis mouse model (24). A recent study in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells showed that YKL-39-activated signal transduction was regulated through the phosphorylation of ERK1/ERK2 kinases (25). YKL-39 was later reported to enhance cell proliferation, colony formation, and type II collagen expression in mouse chondrogenic ATDC5 cells (26).…”

mentioning

confidence: 99%

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

Ranok

Wongsantichon

Robinson

et al. 2015

Journal of Biological Chemistry

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Background: Human YKL-39 is currently recognized as a biomarker for osteoarthritis. Results: Crystal structures of YKL-39 reveal that chitooligosaccharide induces local conformational changes to stabilize sugar⅐protein complexes and that the protein contains five binding subsites for sugars. Conclusion: YKL-39 binds to chitooligosaccharide through enthalpic reactions. Significance: Our findings suggest how YKL-39 interacts with GlcNAc moieties of the natural ligands, which may possibly activate local tissue inflammation.

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Chitinase 3-like protein 2 (CHI3L2, YKL-39) activates phosphorylation of extracellular signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells

Cited by 22 publications

References 22 publications

Two Closely Related Human Members of Chitinase-like Family, CHI3L1 and CHI3L2, Activate ERK1/2 in 293 and U373 Cells but Have the Different Influence on Cell Proliferation

Two Closely Related Human Members of Chitinase-like Family, CHI3L1 and CHI3L2, Activate ERK1/2 in 293 and U373 Cells but Have the Different Influence on Cell Proliferation

Multifunctional Receptor Stabilin-1 in Homeostasis and Disease

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

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