We have found that MIM-B, a putative metastasis suppressor protein, is implicated in actin cytoskeletal control and interaction with a protein tyrosine phosphatase (PTP). MIM was originally described as a protein whose mRNA was Missing in Metastasis, as it was found not to be present in metastatic bladder carcinoma cell lines [Lee, Y.G., Macoska, J.A., Korenchuk, S. and Pienta, K.J. (2002) Neoplasia 4, 291–294]. We further characterized a variant of MIM, which we call MIM-B, and which we believe may be a link between tyrosine kinase signalling and the actin cytoskeleton. We have shown, using purified proteins and cell extracts, that MIM-B is an actin-binding protein, probably via a WASP (Wiskott–Aldrich syndrome protein)-homology 2 domain at its C-terminus. We have also found that MIM-B binds to the cytoplasmic domain of receptor PTPδ. Expression of full-length MIM-B induces actin-rich protrusions resembling microspikes and lamellipodia at the plasma membrane and promotes disassembly of actin stress fibres. The C-terminal portion of MIM-B is localized in the cytoplasm and does not affect the actin cytoskeleton when expressed, while the N-terminal portion localizes to internal vesicles and probably targets the protein to membranes. We postulate that MIM-B may be a regulator of actin assembly downstream of tyrosine kinase signalling and that this activity may explain the involvement of MIM in the metastasis of cancer cells.
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April 2003
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Research Article|
April 15 2003
MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta
Jacquelyn A. WOODINGS;
Jacquelyn A. WOODINGS
1
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
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Stewart J. SHARP;
Stewart J. SHARP
1
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
2To whom correspondence should be addressed (e-mail L.M.Machesky@bham.ac.uk).
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Laura M. MACHESKY
Laura M. MACHESKY
2
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
2To whom correspondence should be addressed (e-mail L.M.Machesky@bham.ac.uk).
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Publisher: Portland Press Ltd
Received:
December 18 2002
Revision Received:
January 30 2003
Accepted:
February 05 2003
Accepted Manuscript online:
February 05 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 463–471.
Article history
Received:
December 18 2002
Revision Received:
January 30 2003
Accepted:
February 05 2003
Accepted Manuscript online:
February 05 2003
Citation
Jacquelyn A. WOODINGS, Stewart J. SHARP, Laura M. MACHESKY; MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta. Biochem J 15 April 2003; 371 (2): 463–471. doi: https://doi.org/10.1042/bj20021962
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