MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase δ
MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase δ
复制标题
DOI：
10.1042/bj20021962
复制
发表时间：
2003-04-15
影响因子：
4.1
通讯作者：
Machesky, LM
中科院分区：
文献类型：
--
作者：
Woodings, JA;Sharp, SJ;Machesky, LM
我们发现MIM-B（一种推定的转移抑制蛋白）参与肌动蛋白细胞骨架控制以及与蛋白质酪氨酸磷酸酶（PTP）的相互作用。MIM最初被描述为其mRNA在转移中缺失的蛋白质，因为发现其不存在于转移性膀胱癌细胞系中[Lee，Y. G.，Macoska，J. A.，Korenchuk，S.和Pienta，K. J.（2002）Neoplasia 4，291-294]。我们进一步表征了MIM的变体，我们称之为MIM-B，我们认为它可能是酪氨酸激酶信号传导和肌动蛋白细胞骨架之间的联系。我们已经表明，使用纯化的蛋白质和细胞提取物，MIM-B是一种肌动蛋白结合蛋白，可能通过WASP（Wiskott-Aldrich综合征蛋白）同源2域在其C-末端。我们还发现，MIM-B结合到受体PTP δ的胞质结构域。全长MIM-B的表达诱导肌动蛋白丰富的突起，类似于质膜上的微刺和片状伪足，并促进肌动蛋白应力纤维的分解。MIM-B的C-末端部分定位于细胞质中，并且在表达时不影响肌动蛋白细胞骨架，而N-末端部分定位于内部囊泡并且可能将蛋白质靶向膜。我们推测MIM-B可能是酪氨酸激酶信号转导下游肌动蛋白组装的调节剂，这种活性可以解释MIM参与癌细胞转移的原因。
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.