MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta.
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 PTPdelta. 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.
Woodings
Jacquelyn A
JA
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Sharp
Stewart J
SJ
Machesky
Laura M
LM
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
D000199:Actins; C486778:MTSS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D005982:Glutathione Transferase; D017027:Protein Tyrosine Phosphatases; C490395:Ptprd protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2