Liprin β1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, is a new target for the metastasis-associated protein S100A4 (Mts1)
Liprin β1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, is a new target for the metastasis-associated protein S100A4 (Mts1)
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DOI：
10.1074/jbc.m110976200
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发表时间：
2002-02-15
影响因子：
4.8
通讯作者：
Lukanidin, E
中科院分区：
文献类型：
--
作者：
Kriajevska, M;Fischer-Larsen, M;Lukanidin, E
转移相关蛋白S100 A4（Mts 1）诱导原发性肿瘤的侵袭并促进转移。S100 A4属于小钙结合5100蛋白家族，其作为钙信号的转换器参与不同的细胞过程。S100 A4通过与其细胞内靶点、非肌肉肌球蛋白重链和p53的相互作用来调节肿瘤细胞的性质。在这里，我们报告鉴定的S100 A4蛋白，liprin β 1的一个新的分子靶点。Liprin β 1属于白细胞共同抗原相关（LAR）跨膜酪氨酸磷酸酶相互作用蛋白家族，可通过与家族另一成员Liprin α 1相互作用调节LAR蛋白特性。我们通过免疫沉淀分析表明，S100 A4在体内与Liprin β 1特异性相互作用。免疫荧光染色显示S100 A4和liprin β 1共定位于细胞质中，特别是在质膜的突起部位。我们将S100 A4结合位点定位在Liprin β 1分子C末端氨基酸残基938和1005之间。S100 A4结合区含有两个推定的蛋白激酶C和蛋白激酶CK 2磷酸化位点。S100 A4-liprin β 1相互作用导致两种激酶在体外抑制liprin β 1磷酸化。
Metastasis-associated protein S100A4 (Mts1) induces invasiveness of primary tumors and promotes metastasis. S100A4 belongs to the family of small calcium-binding 5100 proteins that are involved in different cellular processes as transducers of calcium signal. S100A4 modulates properties of tumor cells via interaction with its intracellular targets, heavy chain of non-muscle myosin and p53. Here we report identification of a new molecular target of the S100A4 protein, liprin beta1. Liprin beta1 belongs to the family of leukocyte common antigen-related (LAR) transmembrane tyrosine phosphatase-interacting proteins that may regulate LAR protein properties via interaction with another member of the family, liprin alpha1. We showed by the immunoprecipitation analysis that S100A4 interacts specifically with liprin beta1 in vivo. Immunofluorescence staining demonstrated the co-localization of S100A4 and liprin beta1 in the cytoplasm and particularly at the protrusion sites of the plasma membrane. We mapped the S100A4 binding site at the C terminus of the liprin beta1 molecule between amino acid residues 938 and 1005. The S100A4-binding region contains two putative phosphorylation sites by protein kinase C and protein kinase CK2. S100A4-liprin beta1 interaction resulted in the inhibition of liprin beta1 phosphorylation by both kinases in vitro.