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The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading.
Oncogene. 2005 May 12; 24(21):3436-47.O

Abstract

Recently, evidence has been accumulating that inositol and phosphatidylinositol polyphosphate play important roles in a variety of signal transduction systems including membrane traffic, actin cytoskeleton rearrangement and cell motility. In this paper, we show for the first time that the SH2-domain-containing inositol 5-phosphatase (SHIP)-2 binds directly to the hepatocyte growth factor (HGF/SF) receptor, c-Met, via phosphotyrosine 1356. HGF induces the breakdown of cell junctions and the dispersion of colonies of epithelial cells including MDCK cells. Whereas only few lamellipodia are observed in MDCK cells 2 min after stimulation with HGF, both SHIP-2- and SHIP-1-overexpressing cells form large, broad lamellipodia. The number of lamellipodia is 2-4-fold greater than that of mock-transfected MDCK cells in the same time period and SHIP is found to colocalize with actin at the leading edge. Furthermore, overexpression of a catalytic inactive mutant of SHIP-2 suppresses HGF-potentiated cell scattering and cell spreading, although these mutant-expressing cells form enhanced number of lamellipodia 2 min after HGF stimulation. Interestingly, cells expressing a mutant lacking the proline-rich domain of SHIP-2 at the C-terminal form few lamellipodia, but still spread and scatter upon stimulation with HGF at a reduced rate. These data suggest that phosphatase activity is required for HGF-mediated cell spreading and scattering but not for alteration of lamellipodium formation, while the proline-rich region influences lamellipodium formation. Furthermore, treatment with 10 microM of phosphatidylinositol 3 (PI3) kinase inhibitor, LY294002, abrogates HGF-induced cell scattering of SHIP-2-overexpressing cells but not parental HEK293 cells, suggesting that a balance between PI3 kinase and SHIP is important for cell motility.

Authors+Show Affiliations

Institut für Biochemie, Medizinische Hochschule Hannover, OE 4310, Carl-Neuberg-Str. 1, Hannover D-30623, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15735664

Citation

Koch, Alexandra, et al. "The SH2-domian-containing Inositol 5-phosphatase (SHIP)-2 Binds to c-Met Directly Via Tyrosine Residue 1356 and Involves Hepatocyte Growth Factor (HGF)-induced Lamellipodium Formation, Cell Scattering and Cell Spreading." Oncogene, vol. 24, no. 21, 2005, pp. 3436-47.
Koch A, Mancini A, El Bounkari O, et al. The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading. Oncogene. 2005;24(21):3436-47.
Koch, A., Mancini, A., El Bounkari, O., & Tamura, T. (2005). The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading. Oncogene, 24(21), 3436-47.
Koch A, et al. The SH2-domian-containing Inositol 5-phosphatase (SHIP)-2 Binds to c-Met Directly Via Tyrosine Residue 1356 and Involves Hepatocyte Growth Factor (HGF)-induced Lamellipodium Formation, Cell Scattering and Cell Spreading. Oncogene. 2005 May 12;24(21):3436-47. PubMed PMID: 15735664.
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TY - JOUR T1 - The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading. AU - Koch,Alexandra, AU - Mancini,Annalisa, AU - El Bounkari,Omar, AU - Tamura,Teruko, PY - 2005/3/1/pubmed PY - 2005/6/4/medline PY - 2005/3/1/entrez SP - 3436 EP - 47 JF - Oncogene JO - Oncogene VL - 24 IS - 21 N2 - Recently, evidence has been accumulating that inositol and phosphatidylinositol polyphosphate play important roles in a variety of signal transduction systems including membrane traffic, actin cytoskeleton rearrangement and cell motility. In this paper, we show for the first time that the SH2-domain-containing inositol 5-phosphatase (SHIP)-2 binds directly to the hepatocyte growth factor (HGF/SF) receptor, c-Met, via phosphotyrosine 1356. HGF induces the breakdown of cell junctions and the dispersion of colonies of epithelial cells including MDCK cells. Whereas only few lamellipodia are observed in MDCK cells 2 min after stimulation with HGF, both SHIP-2- and SHIP-1-overexpressing cells form large, broad lamellipodia. The number of lamellipodia is 2-4-fold greater than that of mock-transfected MDCK cells in the same time period and SHIP is found to colocalize with actin at the leading edge. Furthermore, overexpression of a catalytic inactive mutant of SHIP-2 suppresses HGF-potentiated cell scattering and cell spreading, although these mutant-expressing cells form enhanced number of lamellipodia 2 min after HGF stimulation. Interestingly, cells expressing a mutant lacking the proline-rich domain of SHIP-2 at the C-terminal form few lamellipodia, but still spread and scatter upon stimulation with HGF at a reduced rate. These data suggest that phosphatase activity is required for HGF-mediated cell spreading and scattering but not for alteration of lamellipodium formation, while the proline-rich region influences lamellipodium formation. Furthermore, treatment with 10 microM of phosphatidylinositol 3 (PI3) kinase inhibitor, LY294002, abrogates HGF-induced cell scattering of SHIP-2-overexpressing cells but not parental HEK293 cells, suggesting that a balance between PI3 kinase and SHIP is important for cell motility. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/15735664/The_SH2_domian_containing_inositol_5_phosphatase__SHIP__2_binds_to_c_Met_directly_via_tyrosine_residue_1356_and_involves_hepatocyte_growth_factor__HGF__induced_lamellipodium_formation_cell_scattering_and_cell_spreading_ L2 - https://doi.org/10.1038/sj.onc.1208558 DB - PRIME DP - Unbound Medicine ER -