MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta

Woodings, J. A., Sharp, S. J. and Machesky, L. M. (2003) MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta. Biochemical Journal, 371(2), pp. 463-471. (doi: 10.1042/bj20021962) (PMID:12570871) (PMCID:PMC1223315)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura
Authors: Woodings, J. A., Sharp, S. J., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Biochemical Journal
Publisher:Portland Press
ISSN (Online):1470-8728
Published Online:05 February 2003

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