Adhesion signaling by a novel mitotic substrate of src kinases Journal Article
| Authors: | Bhatt, A. S.; Erdjument-Bromage, H.; Tempst, P.; Craik, C. S.; Moasser, M. M. |
| Article Title: | Adhesion signaling by a novel mitotic substrate of src kinases |
| Abstract: | Src kinases are activated and relocalize to the cytoplasm during mitosis, but their mitotic function has remained elusive. We describe here a novel mitotic substrate of src kinases. Trask (transmembrane and associated with src kinases) is a 140 kDa type I transmembrane glycoprotein unrelated to currently known protein families. Src kinases phosphorylate Trask in vitro and mediate its mitotic hyperphosphorylation in vivo. Trask associates with both yes and src, is localized to the cell membrane during interphase, and undergoes cytoplasmic relocalization during mitosis. Overexpression of Trask leads to cell rounding and a loss of adhesion phenotype. Consistent with a function in cell adhesion, Trask interacts with a number of adhesion and matrix proteins including cadherins, syndecans, and the membrane-type serine protease 1 (MT-SP1), and is proteolytically cleaved by MT-SP1. Trask is unique among cell adhesion molecules in that it is under cell cycle regulation and thus links src kinases with the mitotic regulation of cell adhesion. This suggests a potential pathway by which hyperactive src kinases in tumors can deregulate adhesion signaling and mediate the metastatic phenotype. © 2005 Nature Publishing Group. All rights reserved. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; molecular genetics; protein function; mitosis; metabolism; cell cycle; cell division; metastasis; protein protein interaction; down-regulation; enzyme activation; in vitro study; tumor cells, cultured; enzyme activity; enzyme substrate; protein tyrosine kinase; breast neoplasms; phosphorylation; physiology; carcinogenesis; enzyme phosphorylation; amino acid sequence; molecular sequence data; cell culture; nucleotide sequence; breast tumor; membrane protein; cell membrane; cell adhesion molecules; down regulation; enzyme kinetics; protein family; cell cycle regulation; src-family kinases; isolation and purification; cadherin; cell adhesion; enzyme localization; matrix protein; cell adhesion molecule; src; isoenzyme; interphase; cdcp1; matriptase; mt-sp1; trask; yes; syndecan; transmembrane and associated with src kinase; trask protein, human |
| Journal Title: | Oncogene |
| Volume: | 24 |
| Issue: | 34 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-08-01 |
| Start Page: | 5333 |
| End Page: | 5343 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1208582 |
| PUBMED: | 16007225 |
| PROVIDER: | scopus |
| PMCID: | PMC3023961 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 51" - "Export Date: 24 October 2012" - "CODEN: ONCNE" - "Molecular Sequence Numbers: GENBANK: AY167484;" - "Source: Scopus" |
