Serra-Pagès C, Kedersha N L, Fazikas L, Medley Q, Debant A, Streuli M
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
EMBO J. 1995 Jun 15;14(12):2827-38. doi: 10.1002/j.1460-2075.1995.tb07282.x.
Focal adhesions are sites of cell-extracellular matrix interactions that function in anchoring stress fibers to the plasma membrane and in adhesion-mediated signal transduction. Both focal adhesion structure and signaling ability involve protein tyrosine phosphorylation. LAR is a broadly expressed transmembrane protein tyrosine phosphatase comprised of a cell adhesion-like ectodomain and two intracellular protein tyrosine phosphatase domains. We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAR-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions. Both LAR and LIP.1 decorate the ends of focal adhesions most proximal to the cell nucleus and are excluded from the distal ends of focal adhesions, thus localizing to regions of focal adhesions presumably undergoing disassembly. We propose that LAR and LIP.1 may regulate the disassembly of focal adhesions and thus help orchestrate cell-matrix interactions.
粘着斑是细胞与细胞外基质相互作用的位点，其功能是将应力纤维锚定到质膜上，并参与粘着介导的信号转导。粘着斑的结构和信号传导能力都涉及蛋白质酪氨酸磷酸化。LAR是一种广泛表达的跨膜蛋白酪氨酸磷酸酶，由一个细胞粘附样胞外结构域和两个细胞内蛋白酪氨酸磷酸酶结构域组成。我们鉴定出一种新的细胞质160 kDa磷酸丝氨酸蛋白，称为LAR相互作用蛋白1（LIP.1），它与LAR膜远端的D2蛋白酪氨酸磷酸酶结构域结合，似乎将LAR定位到粘着斑。LAR和LIP.1都分布在粘着斑最靠近细胞核的末端，而被排除在粘着斑的远端，因此定位在可能正在进行解体的粘着斑区域。我们提出，LAR和LIP.1可能调节粘着斑的解体，从而有助于协调细胞与基质的相互作用。
