© The Rockefeller University Press,
0021-9525/1998//1675 $5.00
The Journal of Cell Biology, Volume 141, Number 7,
, 1998 1675-1684
The Laminin–Nidogen Complex is a Ligand for a Specific Splice Isoform of the Transmembrane Protein Tyrosine Phosphatase LAR
Pauline O'Grady,
Tran Cam Thai, and
Haruo Saito
Dana-Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
Leukocyte antigen–related protein (LAR) is a prototype for a family of transmembrane protein tyrosine phosphatases whose extracellular domain is composed of three Ig and several fibronectin type III (FnIII) domains. Complex alternative splicing of the LAR-FnIII domains 4–8 has been observed. The extracellular matrix laminin–nidogen complex was identified as a ligand for the LAR-FnIII domain 5 (Fn5) using a series of GST-LAR-FnIII domain fusion proteins and testing them in in vitro ligand-binding assays. LAR– laminin–nidogen binding was regulated by alternative splicing of a small exon within the LAR-Fn5 so that inclusion of this exon sequence resulted in disruption of the laminin–nidogen-binding activity. Long cellular processes were observed when HeLa cells were plated on laminin–nidogen, but not when plated on a fibronectin surface. Indirect immunofluorescent antibody staining revealed high expression of LAR in a punctate pattern, throughout the length of these cellular processes observed on laminin–nidogen. Antibody-induced cross-linking of LAR inhibited formation of these cellular processes, and inhibition was correlated with changes in cellular actin cytoskeletal structure. Thus, LAR–laminin–nidogen binding may play a role in regulating cell signaling induced by laminin–nidogen, resulting in cell morphological changes.
Abbreviations used in this paper: CAM, cell adhesion molecule; ECM, extracellular matrix; EHS, Engelbreth-Holm-Swarm; FnIII, fibronectin type III domain; GST, glutathione S-transferase; HBS, Hepes buffered saline; LAR, leukocyte antigen–related protein; PTPase, protein tyrosine phosphatase.
Address all correspondence to Dr. Haruo Saito, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Tel.: 617-632-3814; FAX: 617-632-4569; E-mail: haruo_saito{at}dfci.harvard.edu

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Hofmeyer, K., Treisman, J. E.
(2009). The receptor protein tyrosine phosphatase LAR promotes R7 photoreceptor axon targeting by a phosphatase-independent signaling mechanism. Proc. Natl. Acad. Sci. USA
106: 19399-19404
[Abstract]
[Full Text]
-
Kakazu, A., Sharma, G., Bazan, H. E. P.
(2008). Association of Protein Tyrosine Phosphatases (PTPs)-1B with c-Met Receptor and Modulation of Corneal Epithelial Wound Healing. IOVS
49: 2927-2935
[Abstract]
[Full Text]
-
Stryker, E., Johnson, K. G.
(2007). LAR, liprin {alpha} and the regulation of active zone morphogenesis. J. Cell Sci.
120: 3723-3728
[Abstract]
[Full Text]
-
Haapasalo, A., Kim, D. Y., Carey, B. W., Turunen, M. K., Pettingell, W. H., Kovacs, D. M.
(2007). Presenilin/{gamma}-Secretase-mediated Cleavage Regulates Association of Leukocyte-Common Antigen-related (LAR) Receptor Tyrosine Phosphatase with beta-Catenin. J. Biol. Chem.
282: 9063-9072
[Abstract]
[Full Text]
-
Lee, S., Faux, C., Nixon, J., Alete, D., Chilton, J., Hawadle, M., Stoker, A. W.
(2007). Dimerization of Protein Tyrosine Phosphatase {sigma} Governs both Ligand Binding and Isoform Specificity. Mol. Cell. Biol.
27: 1795-1808
[Abstract]
[Full Text]
-
Siu, R., Fladd, C., Rotin, D.
(2007). N-Cadherin Is an In Vivo Substrate for Protein Tyrosine Phosphatase Sigma (PTP{sigma}) and Participates in PTP{sigma}-Mediated Inhibition of Axon Growth. Mol. Cell. Biol.
27: 208-219
[Abstract]
[Full Text]
-
Sallee, J. L., Wittchen, E. S., Burridge, K.
(2006). Regulation of Cell Adhesion by Protein-tyrosine Phosphatases: II. CELL-CELL ADHESION. J. Biol. Chem.
281: 16189-16192
[Abstract]
[Full Text]
-
Uetani, N., Chagnon, M. J., Kennedy, T. E., Iwakura, Y., Tremblay, M. L.
(2006). Mammalian motoneuron axon targeting requires receptor protein tyrosine phosphatases sigma and delta.. J. Neurosci.
26: 5872-5880
[Abstract]
[Full Text]
-
Machide, M., Hashigasako, A., Matsumoto, K., Nakamura, T.
(2006). Contact Inhibition of Hepatocyte Growth Regulated by Functional Association of the c-Met/Hepatocyte Growth Factor Receptor and LAR Protein-tyrosine Phosphatase. J. Biol. Chem.
281: 8765-8772
[Abstract]
[Full Text]
-
Adato, A., Lefevre, G., Delprat, B., Michel, V., Michalski, N., Chardenoux, S., Weil, D., El-Amraoui, A., Petit, C.
(2005). Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. Hum Mol Genet
14: 3921-3932
[Abstract]
[Full Text]
-
Ackley, B. D., Harrington, R. J., Hudson, M. L., Williams, L., Kenyon, C. J., Chisholm, A. D., Jin, Y.
(2005). The Two Isoforms of the Caenorhabditis elegans Leukocyte-Common Antigen Related Receptor Tyrosine Phosphatase PTP-3 Function Independently in Axon Guidance and Synapse Formation. J. Neurosci.
25: 7517-7528
[Abstract]
[Full Text]
-
Stoker, A. W
(2005). Protein tyrosine phosphatases and signalling. J Endocrinol
185: 19-33
[Abstract]
[Full Text]
-
Hathaway, H. J., Evans, S. C., Dubois, D. H., Foote, C. I., Elder, B. H., Shur, B. D.
(2003). Mutational analysis of the cytoplasmic domain of {beta}1,4-galactosyltransferase I: influence of phosphorylation on cell surface expression. J. Cell Sci.
116: 4319-4330
[Abstract]
[Full Text]
-
Krueger, N. X., Reddy, R. S., Johnson, K., Bateman, J., Kaufmann, N., Scalice, D., Van Vactor, D., Saito, H.
(2003). Functions of the Ectodomain and Cytoplasmic Tyrosine Phosphatase Domains of Receptor Protein Tyrosine Phosphatase Dlar In Vivo. Mol. Cell. Biol.
23: 6909-6921
[Abstract]
[Full Text]
-
Toledano-Katchalski, H., Tiran, Z., Sines, T., Shani, G., Granot-Attas, S., den Hertog, J., Elson, A.
(2003). Dimerization In Vivo and Inhibition of the Nonreceptor Form of Protein Tyrosine Phosphatase Epsilon. Mol. Cell. Biol.
23: 5460-5471
[Abstract]
[Full Text]
-
van der Wijk, T., Blanchetot, C., Overvoorde, J., den Hertog, J.
(2003). Redox-regulated Rotational Coupling of Receptor Protein-tyrosine Phosphatase alpha Dimers. J. Biol. Chem.
278: 13968-13974
[Abstract]
[Full Text]
-
Johnson, K. G., Van Vactor, D.
(2003). Receptor Protein Tyrosine Phosphatases in Nervous System Development. Physiol. Rev.
83: 1-24
[Abstract]
[Full Text]
-
Tsujikawa, K., Ichijo, T., Moriyama, K., Tadotsu, N., Sakamoto, K., Sakane, N., Fukada, S.-i., Furukawa, T., Saito, H., Yamamoto, H.
(2002). Regulation of Lck and Fyn Tyrosine Kinase Activities by Transmembrane Protein Tyrosine Phosphatase Leukocyte Common Antigen-Related Molecule. Mol Cancer Res
1: 155-163
[Abstract]
[Full Text]
-
Aricescu, A. R., McKinnell, I. W., Halfter, W., Stoker, A. W.
(2002). Heparan Sulfate Proteoglycans Are Ligands for Receptor Protein Tyrosine Phosphatase {sigma}. Mol. Cell. Biol.
22: 1881-1892
[Abstract]
[Full Text]
-
Kriajevska, M., Fischer-Larsen, M., Moertz, E., Vorm, O., Tulchinsky, E., Grigorian, M., Ambartsumian, N., Lukanidin, E.
(2002). Liprin beta 1, a Member of the Family of LAR Transmembrane Tyrosine Phosphatase-interacting Proteins, Is a New Target for the Metastasis-associated Protein S100A4 (Mts1). J. Biol. Chem.
277: 5229-5235
[Abstract]
[Full Text]
-
Harrington, R. J., Gutch, M. J., Hengartner, M. O., Tonks, N. K., Chisholm, A. D.
(2002). The C. elegans LAR-like receptor tyrosine phosphatase PTP-3 and the VAB-1 Eph receptor tyrosine kinase have partly redundant functions in morphogenesis. Development
129: 2141-2153
[Abstract]
[Full Text]
-
Bonner, J., O'Connor, T. P.
(2001). The Permissive Cue Laminin Is Essential for Growth Cone Turning In Vivo. J. Neurosci.
21: 9782-9791
[Abstract]
[Full Text]
-
Xie, Y., Yeo, T. T., Zhang, C., Yang, T., Tisi, M. A., Massa, S. M., Longo, F. M.
(2001). The Leukocyte Common Antigen-Related Protein Tyrosine Phosphatase Receptor Regulates Regenerative Neurite Outgrowth In Vivo. J. Neurosci.
21: 5130-5138
[Abstract]
[Full Text]
-
Tsujikawa, K., Kawakami, N., Uchino, Y., Ichijo, T., Furukawa, T., Saito, H., Yamamoto, H.
(2001). Distinct Functions of the Two Protein Tyrosine Phosphatase Domains of LAR (Leukocyte Common Antigen-Related) on Tyrosine Dephosphorylation of Insulin Receptor. Mol. Endocrinol.
15: 271-280
[Abstract]
[Full Text]
-
Jiang, G., den Hertog, J., Hunter, T.
(2000). Receptor-Like Protein Tyrosine Phosphatase alpha Homodimerizes on the Cell Surface. Mol. Cell. Biol.
20: 5917-5929
[Abstract]
[Full Text]
-
Blanchetot, C., den Hertog, J.
(2000). Multiple Interactions between Receptor Protein-tyrosine Phosphatase (RPTP) alpha and Membrane-distal Protein-tyrosine Phosphatase Domains of Various RPTPs. J. Biol. Chem.
275: 12446-12452
[Abstract]
[Full Text]
-
Yang, T., Martignetti, J. A., Massa, S. M., Longo, F. M.
(2000). Leukocyte common-antigen-related tyrosine phosphatase receptor: altered expression of mRNA and protein in the New England Deaconess Hospital rat line exhibiting spontaneous pheochromocytoma. Carcinogenesis
21: 125-131
[Abstract]
[Full Text]
-
Petrone, A, Sap, J
(2000). Emerging issues in receptor protein tyrosine phosphatase function: lifting fog or simply shifting?. J. Cell Sci.
113: 2345-2354
[Abstract]
-
Ledig, M. M., Haj, F., Bixby, J. L., Stoker, A. W., Mueller, B. K.
(1999). The Receptor Tyrosine Phosphatase Cryp{alpha} Promotes Intraretinal Axon Growth. JCB
147: 375-388
[Abstract]
[Full Text]
-
Lee, Y.-J., Streuli, C. H.
(1999). Extracellular Matrix Selectively Modulates the Response of Mammary Epithelial Cells to Different Soluble Signaling Ligands. J. Biol. Chem.
274: 22401-22408
[Abstract]
[Full Text]
-
Kruger, R. P., Goodyear, R. J., Legan, P. K., Warchol, M. E., Raphael, Y., Cotanche, D. A., Richardson, G. P.
(1999). The Supporting-Cell Antigen: A Receptor-Like Protein Tyrosine Phosphatase Expressed in the Sensory Epithelia of the Avian Inner Ear. J. Neurosci.
19: 4815-4827
[Abstract]
[Full Text]
-
Grassi, M, Moens, G, Rousselle, P, Thiery, J., Jouanneau, J
(1999). The SFL activity secreted by metastatic carcinoma cells is related to laminin 5 and mediates cell scattering in an integrin-independent manner. J. Cell Sci.
112: 2511-2520
[Abstract]