Advanced

Individual domains of Tensin2 exhibit distinct subcellular localisations and migratory effects.

Hafizi, Sassan LU ; Sernstad, Emma; Swinny, Jerome D; Gomez, Maria LU and Dahlbäck, Björn LU (2010) In International Journal of Biochemistry and Cell Biology 42. p.52-61
Abstract
Tensins are large intracellular proteins believed to link the extracellular matrix to the cytoskeleton via integrins. Tensins are multidomain proteins consisting of homologous C1, PTPase, C2, SH2 and PTB domains. Full-length Tensin proteins can undergo cleavage inside cells, thus yielding domains in isolation that may have discrete subcellular localisations and downstream effects. We expressed different isoforms of Tensin2 and their individual domains as recombinant green fluorescent protein (GFP)-fusion constructs in DU145 human prostate cancer cells. Under fluorescence confocal microscopy, the isolated domains of Tensin2 all displayed discrete distributions throughout the cytoplasm and the nucleus. In particular, partial constructs... (More)
Tensins are large intracellular proteins believed to link the extracellular matrix to the cytoskeleton via integrins. Tensins are multidomain proteins consisting of homologous C1, PTPase, C2, SH2 and PTB domains. Full-length Tensin proteins can undergo cleavage inside cells, thus yielding domains in isolation that may have discrete subcellular localisations and downstream effects. We expressed different isoforms of Tensin2 and their individual domains as recombinant green fluorescent protein (GFP)-fusion constructs in DU145 human prostate cancer cells. Under fluorescence confocal microscopy, the isolated domains of Tensin2 all displayed discrete distributions throughout the cytoplasm and the nucleus. In particular, partial constructs containing the C1 domain localised preferentially to the nucleus, including the isolated C1 domain and the PTPase domain. In contrast, all three full-length isoforms of Tensin2 were present exclusively in discrete punctate bodies throughout the cytoplasm. This punctate staining showed colocalisation with the tumour suppressor protein DLC-1 as well as with actin (phalloidin). Furthermore, DU145 cells transiently expressing partial Tensin2 constructs containing the PTB domain showed an increased haptotactic migration. In addition, stimulation of renal carcinoma cells stably expressing Tensin2 by the survival factor Gas6 caused phosphorylation of its receptor Axl, but no effect on Tensin2, which was already maximally phosphorylated at time 0. In conclusion, our results indicate that differential proteolytic cleavage of Tensin2 can liberate domains with discrete localisations and functions, which has implications for the role of Tensins in cancer cell survival and motility. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Biochemistry and Cell Biology
volume
42
pages
52 - 61
publisher
Elsevier
external identifiers
  • wos:000273912200009
  • pmid:19747564
  • scopus:70549111595
ISSN
1878-5875
DOI
10.1016/j.biocel.2009.09.005
language
English
LU publication?
yes
id
008b0c34-63f3-4037-95e5-7c62e2993262 (old id 1483562)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19747564?dopt=Abstract
date added to LUP
2009-10-07 11:00:35
date last changed
2017-01-01 07:49:43
@article{008b0c34-63f3-4037-95e5-7c62e2993262,
  abstract     = {Tensins are large intracellular proteins believed to link the extracellular matrix to the cytoskeleton via integrins. Tensins are multidomain proteins consisting of homologous C1, PTPase, C2, SH2 and PTB domains. Full-length Tensin proteins can undergo cleavage inside cells, thus yielding domains in isolation that may have discrete subcellular localisations and downstream effects. We expressed different isoforms of Tensin2 and their individual domains as recombinant green fluorescent protein (GFP)-fusion constructs in DU145 human prostate cancer cells. Under fluorescence confocal microscopy, the isolated domains of Tensin2 all displayed discrete distributions throughout the cytoplasm and the nucleus. In particular, partial constructs containing the C1 domain localised preferentially to the nucleus, including the isolated C1 domain and the PTPase domain. In contrast, all three full-length isoforms of Tensin2 were present exclusively in discrete punctate bodies throughout the cytoplasm. This punctate staining showed colocalisation with the tumour suppressor protein DLC-1 as well as with actin (phalloidin). Furthermore, DU145 cells transiently expressing partial Tensin2 constructs containing the PTB domain showed an increased haptotactic migration. In addition, stimulation of renal carcinoma cells stably expressing Tensin2 by the survival factor Gas6 caused phosphorylation of its receptor Axl, but no effect on Tensin2, which was already maximally phosphorylated at time 0. In conclusion, our results indicate that differential proteolytic cleavage of Tensin2 can liberate domains with discrete localisations and functions, which has implications for the role of Tensins in cancer cell survival and motility.},
  author       = {Hafizi, Sassan and Sernstad, Emma and Swinny, Jerome D and Gomez, Maria and Dahlbäck, Björn},
  issn         = {1878-5875},
  language     = {eng},
  pages        = {52--61},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry and Cell Biology},
  title        = {Individual domains of Tensin2 exhibit distinct subcellular localisations and migratory effects.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2009.09.005},
  volume       = {42},
  year         = {2010},
}