Lipsky B P, Beals C R, Staunton D E
ICOS Corporation, Bothell, Washington 98021, USA.
J Biol Chem. 1998 May 8;273(19):11709-13. doi: 10.1074/jbc.273.19.11709.
We have identified a novel cytoplasmic protein, leupaxin, that is preferentially expressed in hematopoietic cells and is most homologous to the focal adhesion protein, paxillin. Leupaxin possesses two types of protein interaction domains. There are four carboxyl-terminal LIM domains in leupaxin that share 70% amino acid identity and 80% similarity with those in paxillin. Paxillin LIM domains mediate localization to focal contacts. In the amino-terminal region of leupaxin there are three short stretches of approximately 13 amino acids that share 70-90% similarity with paxillin LD motifs. Paxillin LD motifs have been implicated in focal adhesion kinase (FAK) and vinculin binding resulting in the localization of FAK to focal adhesions. Leupaxin is expressed in cell types, such as macrophage, that lack FAK. We demonstrate here that leupaxin associates with a second FAK family member, PYK2. As leupaxin and PYK2 are both preferentially expressed in leukocytes they may therefore form a cell type-specific signaling complex. We also demonstrate that leupaxin is a substrate for a tyrosine kinase in lymphoid cells and thus may function in and be regulated by tyrosine kinase activity. Leupaxin is thus a phosphotyrosine protein with LD and LIM binding motifs most homologous to paxillin that may assemble and regulate PYK2 signaling complexes in leukocytes.
我们鉴定出一种新的细胞质蛋白——白细胞Paxin，它在造血细胞中优先表达，并且与粘着斑蛋白桩蛋白最为同源。白细胞Paxin具有两种类型的蛋白质相互作用结构域。白细胞Paxin的羧基末端有四个LIM结构域，与桩蛋白中的LIM结构域具有70%的氨基酸同一性和80%的相似性。桩蛋白的LIM结构域介导其定位于粘着斑。在白细胞Paxin的氨基末端区域，有三段约13个氨基酸的短序列，与桩蛋白的LD基序具有70%-90%的相似性。桩蛋白的LD基序与粘着斑激酶（FAK）和纽蛋白结合有关，从而导致FAK定位于粘着斑。白细胞Paxin在缺乏FAK的细胞类型（如巨噬细胞）中表达。我们在此证明白细胞Paxin与FAK家族的另一个成员PYK2相关联。由于白细胞Paxin和PYK2都优先在白细胞中表达，因此它们可能形成一种细胞类型特异性的信号复合物。我们还证明白细胞Paxin是淋巴细胞中一种酪氨酸激酶的底物，因此可能在酪氨酸激酶活性中发挥作用并受其调节。因此，白细胞Paxin是一种磷酸酪氨酸蛋白，具有与桩蛋白最同源的LD和LIM结合基序，可能在白细胞中组装并调节PYK2信号复合物。
