Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
*Author for correspondence (e-mail: benny.geiger{at}weizmann.ac.il)
![]() |
SUMMARY |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: Focal contacts, Focal adhesions, Cytoskeleton, Adhesion-mediated signalling, Extracellular matrix
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Complexity |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Following the biochemical tradition, many research groups have attempted to characterize the interactions between the different focal contact molecules, hoping that such information might help us understand how this molecular ensemble works. Such in vitro binding studies have revealed a multitude of protein-protein interactions that might take place in these contact sites (Fig. 1). Some of the interactions within focal contacts are mediated by known binding motifs, such as SH2 and SH3 domains, which serve as specific docking sites for tyrosine-phosphorylated proteins (which can be regulated by kinases and phosphatases) and proline-rich domains, respectively. For example, FAK contains tyrosines that upon phosphorylation can bind to the SH2 domains of several molecules, including Src kinases, Csk, PTEN, Grb2, Grb7 and PI 3-kinase, and proline-rich domains that can bind to Cas, Graf, PSGAP and PLC-. Obviously, FAK cannot be engaged with all these molecules simultaneously, and the mechanism by which it selects its partners is obscure. Equally unclear are the specificity and susceptibility to external regulation of the other types of molecular interaction (direct binding or other regulatory interactions) that might occur in focal contacts (interconnecting lines in Fig. 1).
Since most components of focal adhesions contain multiple binding sites for other components, the molecular ensemble can, theoretically, assemble in numerous alternative ways, thus giving rise to many different supramolecular structures. Therefore, the regulation of the various interactions between the components in vivo plays a key role in defining the structure and function of focal contacts. To illustrate the significance of regulating the binding activities of different sites in these multidomain proteins, we would like to discuss the properties of one of the most prominent residents of focal contacts, namely vinculin (Fig. 2). Electron microscopy indicated that vinculin contains a globular head and a long flexible tail (Milam, 1985; Molony and Burridge, 1985; Winkler et al., 1996). The head region contains binding sites for -actinin (Kroemker et al., 1994; Wachsstock et al., 1987) and talin (Burridge and Mangeat, 1984; Johnson and Craig, 1994), as well as an intramolecular binding site for the vinculin tail (Johnson and Craig, 1994; Miller et al., 2001; Weekes et al., 1996). The vinculin tail can bind not only to the vinculin head but also to paxillin (Turner et al., 1990; Wood et al., 1994), F-actin (Huttelmaier et al., 1997; Jockusch and Isenberg, 1981; Wilkins and Lin, 1982), phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2 (Fukami et al., 1994; Johnson et al., 1998; Niggli and Gimona, 1993; Sechi et al., 2000)] and the lipid bilayer proper (Bakolitsa et al., 1999; Johnson et al., 1998) (Fig. 2A). The head and tail of vinculin are connected through a proline-rich neck, which can bind to VASP (Brindle et al., 1996; Reinhard et al., 1996), ponsin (Mandai et al., 1999) and vinexin (Kioka et al., 1999) (Fig. 2A). Interestingly, the intramolecular interaction between the head and the tail of vinculin masks the binding sites for
-actinin (Kroemker et al., 1994), talin (Johnson and Craig, 1994), F-actin (Johnson and Craig, 1995) and VASP (Huttelmaier et al., 1998), and therefore prevents vinculin from binding to these proteins (Fig. 2B). Transition from a closed to an open conformation is induced by the binding of PtdIns(4,5)P2 to the vinculin tail (Gilmore and Burridge, 1996; Weekes et al., 1996) (Fig. 2B). Thus, upon activation by PtdIns(4,5)P2, vinculin appears to facilitate the assembly of focal contacts by crosslinking and recruiting its various partners (Fig. 2C). Such PtdIns(4,5)P2-mediated activation of vinculin might be induced for example by Rho, which activates the PI4P5-kinase that catalyzes the synthesis of PtdIns(4,5)P2.
|
![]() |
Diversity |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To gain insight into this issue, we used quantitative fluorescence microscopy to explore variations in the structure and molecular composition of cell-matrix adhesions (Katz et al., 2000; Zamir et al., 1999). In cultured fibroblasts, we noted striking differences between classical focal contacts - oval, peripheral structures enriched with vß3-integrin, paxillin, vinculin and tyrosine-phosphorylated proteins - and fibrillar adhesions, which are elongated or dot-like, central structures containing
5ß1-integrin, tensin and parvin/actopaxin and attached to fibronectin fibrils (Fig. 3) (Katz et al., 2000; Olski et al., 2001; Zamir et al., 1999). Beside the sharp differences between focal contacts and fibrillar adhesions, there are more subtle variations in their molecular compositions. This is manifested by variations in the relative fluorescence labeling intensities for different proteins, evident through fluorescence ratio imaging (Katz et al., 2000; Zamir et al., 1999). Further characterization of matrix adhesion heterogeneity, to determine its structural and functional significance, is therefore necessary.
|
Focal complexes normally develop into focal contacts as a consequence of the activation of Rho (Clark et al., 1998; Rottner et al., 1999) or following the application of external force (Riveline et al., 2001). Active Rho has multiple targets (Bishop and Hall, 2000), but the combined action of just two of them, Rho kinase and Diaphanous (Dia1), appears to induce the transition of focal complexes into focal contacts. This conclusion is based on their capacity to restore stress fiber and focal contact formation in cells expressing Botulinum C3 transferase, which specifically inactivates Rho (Watanabe et al., 1999).
Podosomes are another form of integrin-mediated adhesion (David-Pfeuty and Singer, 1980; Marchisio et al., 1984; Tarone et al., 1985). They were first described as aberrant matrix adhesions formed in Rous-sarcoma-virus-transformed cells. They are small (0.5 µm) cylindrical structures containing an actin core surrounded by tyrosine phosphorylated proteins and several typical focal contact proteins, such as vinculin and talin. The precise molecular composition and organization of podosomes is unclear. Podosomes are present in a variety of normal cells, such as monocytes and macrophages, in which they are apparently involved in cell motility, and osteoclasts, in which they aggregate in the sealing zone at the periphery of the cell and play a role in bone resorption (Duong et al., 1998; Lakkakorpi et al., 1999; Wesolowski et al., 1995). The development of podosomes appears to be regulated by a variety of signaling and cytoskeletal systems, including the microtubular system (Linder et al., 2000) and those involving dynamin (Ochoa et al., 2000), PI 3-kinase (Lakkakorpi et al., 1997) and RhoA (Chellaiah et al., 2000).
The presence of structural variants of matrix adhesions, which have distinct morphologies, compositions and dynamics, may provide important clues to the molecular basis for the variations in structure, assembly and function of the different forms of adhesions. It may also shed light on the interplay between the structure of matrix adhesions and their capacity to activate or respond to specific signaling pathways. Of particular interest are the dynamic processes involved in the formation and transformation of matrix adhesions from one form to the another, which raises several questions. How is Rac involved in assembly of focal complexes, and how is Rho involved in their development into focal contacts? How does activated pp60src convert focal contacts into podosomes? How does mechanical force stimulate focal contact growth, and how do the molecular and structural variations, evident in different adhesions, affect their differential involvement in cell motility, invasion, matrix assembly and growth?
![]() |
Dynamics |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Using GFP fusion proteins containing cytoplasmic components of focal contacts (e.g. paxillin) and fibrillar adhesions (e.g. tensin), we were able to differentially monitor the dynamics of these two structures in living cells (Zamir et al., 2000). Focal contacts, containing GFP-paxillin, grew, faded or translocated centripetally, which is consistent with previous studies. GFP-tensin, by contrast, continuously translocated from peripheral focal contacts towards the cell center, forming fibrillar adhesions (Fig. 4) (Zamir et al., 2000). Studies by Pankov et al. are consistent with this observation and showed, using an antibody-chase technique, that whereas vß3 integrin remains in focal contacts
5ß1 integrin translocates centripetally, which indicated that this process is instrumental in fibronectin fibrillogenesis (Pankov et al., 2000). The translocation of fibrillar adhesions is driven by actomyosin contractility and can be blocked by inhibitors such as H-7, ML-7 and latrunculin-A (Fig. 4) (Zamir et al., 2000). However, in a sharp contrast with focal contacts, which are strictly tension dependent, the maintenance of fibrillar adhesions does not depend on actomyosin contractility (Zamir et al., 1999; Zamir et al., 2000).
|
An important potential element in the regulation of matrix adhesion reorganization is the fine-tuning of local tyrosine phosphorylation. As shown in Fig. 1, several molecular interactions in focal contacts depend on tyrosine-specific phosphorylation of different components of the submembrane plaque. Moreover, phosphorylation and dephosphorylation events can also regulate conformational states of molecules (e.g. pp60src) by modulating SH2-phosphotyrosine interactions (Nada et al., 1991; Williams et al., 1997; Xu et al., 1997). A hint that such a mechanism is involved in the segregation of focal contacts and fibrillar adhesions emerged from a recent study on the organization of cell-matrix adhesions in Src-deficient cells (Volberg et al., 2001). Src-null cells exhibit considerably lower levels of phosphotyrosine in their matrix adhesion sites, compared with their wild-type counterparts, and strikingly, the level of tensin in classical focal contacts is very high. This suggests that the exit of tensin from the focal contacts and the formation of fibrillar adhesions depends on Src-mediated tyrosine phosphorylation.
![]() |
Conclusion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Abercrombie, M. and Dunn, G. A. (1975). Adhesions of fibroblasts to substratum during contact inhibition observed by interference reflection microscopy. Exp. Cell Res. 92, 57-62.[Medline]
Abercrombie, M., Heaysman, J. E. and Pegrum, S. M. (1971). The locomotion of fibroblasts in culture. IV. Electron microscopy of the leading lamella. Exp. Cell Res. 67, 359-367.[Medline]
Bakolitsa, C., de Pereda, J. M., Bagshaw, C. R., Critchley, D. R. and Liddington, R. C. (1999). Crystal structure of the vinculin tail suggests a pathway for activation. Cell 99, 603-613.[Medline]
Beningo, K. A., Dembo, M., Kaverina, I., Small, J. V. and Wang, Y. (2001). Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153, 881-888.
Bishop, A. L. and Hall, A. (2000). Rho GTPases and their effector proteins. Biochem J. 348, 241-255.[Medline]
Bono, P., Rubin, K., Higgins, J. M. and Hynes, R. O. (2001). Layilin, a novel integral membrane protein, is a hyaluronan receptor. Mol. Biol. Cell 12, 891-900.
Borowsky, M. L. and Hynes, R. O. (1998). Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles. J. Cell Biol. 143, 429-442.
Brindle, N. P., Holt, M. R., Davies, J. E., Price, C. J. and Critchley, D. R. (1996). The focal-adhesion vasodilator-stimulated phosphoprotein (VASP) binds to the proline-rich domain in vinculin. Biochem J. 318, 753-757.[Medline]
Burridge, K. and Mangeat, P. (1984). An interaction between vinculin and talin. Nature 308, 744-746.[Medline]
Chellaiah, M. A., Soga, N., Swanson, S., McAllister, S., Alvarez, U., Wang, D., Dowdy, S. F. and Hruska, K. A. (2000). Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J. Biol. Chem. 275, 11993-12002.
Clark, E. A., King, W. G., Brugge, J. S., Symons, M. and Hynes, R. O. (1998). Integrin-mediated signals regulated by members of the rho family of GTPases. J. Cell Biol. 142, 573-586.
David-Pfeuty, T. and Singer, S. J. (1980). Altered distributions of the cytoskeletal proteins vinculin and -actinin in cultured fibroblasts transformed by Rous sarcoma virus. Proc. Natl. Acad. Sci. USA 77, 6687-6691.[Abstract]
Duong, L. T., Lakkakorpi, P. T., Nakamura, I., Machwate, M., Nagy, R. M. and Rodan, G. A. (1998). PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of vß3 integrin, and phosphorylated by src kinase. J. Clin. Invest. 102, 881-892.
Fukami, K., Endo, T., Imamura, M. and Takenawa, T. (1994). -Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase. J. Biol. Chem. 269, 1518-1522.
Geiger, B. and Bershadsky, A. (2001). Assembly and mechanosensory function of focal contacts. Curr. Opin. Cell Biol. 13, 584-592.[Medline]
Gilmore, A. P. and Burridge, K. (1996). Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature 381, 531-535.[Medline]
Harpur, A. G., Wouters, F. S. and Bastiaens, P. I. (2001). Imaging FRET between spectrally similar GFP molecules in single cells. Nat. Biotechnol. 19, 167-169.[Medline]
Huttelmaier, S., Bubeck, P., Rudiger, M. and Jockusch, B. M. (1997). Characterization of two F-actin-binding and oligomerization sites in the cell-contact protein vinculin. Eur. J. Biochem. 247, 1136-1142.[Abstract]
Huttelmaier, S., Mayboroda, O., Harbeck, B., Jarchau, T., Jockusch, B. M. and Rudiger, M. (1998). The interaction of the cell-contact proteins VASP and vinculin is regulated by phosphatidylinositol-4,5-bisphosphate. Curr. Biol. 8, 479-488.[Medline]
Hynes, R. O. (1992). Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69, 11-25.[Medline]
Izzard, C. S. and Lochner, L. R. (1976). Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique. J. Cell Sci. 21, 129-159.[Abstract]
Izzard, C. S. and Lochner, L. R. (1980). Formation of cell-to-substrate contacts during fibroblast motility: an interference-reflexion study. J. Cell Sci. 42, 81-116.[Abstract]
Jockusch, B. M. and Isenberg, G. (1981). Interaction of -actinin and vinculin with actin: opposite effects on filament network formation. Proc. Natl. Acad. Sci. USA 78, 3005-3009.[Abstract]
Johnson, R. P. and Craig, S. W. (1994). An intramolecular association between the head and tail domains of vinculin modulates talin binding. J. Biol. Chem. 269, 12611-12619.
Johnson, R. P. and Craig, S. W. (1995). F-actin binding site masked by the intramolecular association of vinculin head and tail domains. Nature 373, 261-264.[Medline]
Johnson, R. P., Niggli, V., Durrer, P. and Craig, S. W. (1998). A conserved motif in the tail domain of vinculin mediates association with and insertion into acidic phospholipid bilayers. Biochemistry 37, 10211-10222.[Medline]
Kam, Z., Zamir, E. and Geiger, B. (2001). Probing molecular processes in live cells by quantitative multidimensional microscopy. Trends Cell Biol. 11, 329-334.[Medline]
Katz, B. Z., Zamir, E., Bershadsky, A., Kam, Z., Yamada, K. M. and Geiger, B. (2000). Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol. Biol. Cell 11, 1047-1060.
Kioka, N., Sakata, S., Kawauchi, T., Amachi, T., Akiyama, S. K., Okazaki, K., Yaen, C., Yamada, K. M. and Aota, S. (1999). Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization. J. Cell Biol. 144, 59-69.
Kiosses, W. B., Shattil, S. J., Pampori, N. and Schwartz, M. A. (2001). Rac recruits high-affinity integrin vß3 to lamellipodia in endothelial cell migration. Nat. Cell Biol. 3, 316-320.[Medline]
Kroemker, M., Rudiger, A. H., Jockusch, B. M. and Rudiger, M. (1994). Intramolecular interactions in vinculin control -actinin binding to the vinculin head. FEBS Lett. 355, 259-262.[Medline]
Lakkakorpi, P. T., Nakamura, I., Nagy, R. M., Parsons, J. T., Rodan, G. A. and Duong, L. T. (1999). Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone. J. Biol. Chem. 274, 4900-4907.
Lakkakorpi, P. T., Wesolowski, G., Zimolo, Z., Rodan, G. A. and Rodan, S. B. (1997). Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading. Exp. Cell Res. 237, 296-306.[Medline]
Linder, S., Hufner, K., Wintergerst, U. and Aepfelbacher, M. (2000). Microtubule-dependent formation of podosomal adhesion structures in primary human macrophages. J. Cell Sci. 113, 4165-4176.
Mandai, K., Nakanishi, H., Satoh, A., Takahashi, K., Satoh, K., Nishioka, H., Mizoguchi, A. and Takai, Y. (1999). Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions. J. Cell Biol. 144, 1001-1017.
Marchisio, P. C., Cirillo, D., Naldini, L., Primavera, M. V., Teti, A. and Zambonin-Zallone, A. (1984). Cell-substratum interaction of cultured avian osteoclasts is mediated by specific adhesion structures. J. Cell Biol. 99, 1696-1705.[Abstract]
Milam, L. M. (1985). Electron microscopy of rotary shadowed vinculin and vinculin complexes. J. Mol. Biol. 184, 543-545.[Medline]
Miller, G. J., Dunn, S. D. and Ball, E. H. (2001). Interaction of the N- and C-terminal domains of vinculin: characterization and mapping studies. J. Biol. Chem. 276, 11729-11734.
Molony, L. and Burridge, K. (1985). Molecular shape and self-association of vinculin and metavinculin. J. Cell. Biochem. 29, 31-36.[Medline]
Myohanen, H. T., Stephens, R. W., Hedman, K., Tapiovaara, H., Ronne, E., Hoyer-Hansen, G., Dano, K. and Vaheri, A. (1993). Distribution and lateral mobility of the urokinase-receptor complex at the cell surface. J. Histochem. Cytochem. 41, 1291-1301.
Nada, S., Okada, M., MacAuley, A., Cooper, J. A. and Nakagawa, H. (1991). Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src. Nature 351, 69-72.[Medline]
Niggli, V. and Gimona, M. (1993). Evidence for a ternary interaction between -actinin, (meta)vinculin and acidic-phospholipid bilayers. Eur. J. Biochem. 213, 1009-1015.[Abstract]
Nobes, C. D. and Hall, A. (1995). Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53-62.[Medline]
Ochoa, G. C., Slepnev, V. I., Neff, L., Ringstad, N., Takei, K., Daniell, L., Kim, W., Cao, H., McNiven, M., Baron, R. et al. (2000). A functional link between dynamin and the actin cytoskeleton at podosomes. J. Cell Biol. 150, 377-389.
Olski, T. M., Noegel, A. A. and Korenbaum, E. (2001). Parvin, a 42 kDa focal adhesion protein, related to the -actinin superfamily. J. Cell Sci. 114, 525-538.
Pankov, R., Cukierman, E., Katz, B. Z., Matsumoto, K., Lin, D. C., Lin, S., Hahn, C. and Yamada, K. M. (2000). Integrin dynamics and matrix assembly: tensin-dependent translocation of 5ß1 integrins promotes early fibronectin fibrillogenesis. J. Cell Biol. 148, 1075-1090.
Reinhard, M., Rudiger, M., Jockusch, B. M. and Walter, U. (1996). VASP interaction with vinculin: a recurring theme of interactions with proline-rich motifs. FEBS Lett. 399, 103-107.[Medline]
Riveline, D., Zamir, E., Balaban, N. Q., Schwarz, U. S., Ishizaki, T., Narumiya, S., Kam, Z., Geiger, B. and Bershadsky, A. D. (2001). Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153, 1175-1185.
Rottner, K., Hall, A. and Small, J. V. (1999). Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9, 640-648.[Medline]
Schwartz, M. A., Schaller, M. D. and Ginsberg, M. H. (1995). Integrins: emerging paradigms of signal transduction. Annu. Rev. Cell Dev. Biol. 11, 549-599.[Medline]
Sechi, A. S. and Wehland, J. (2000). The actin cytoskeleton and plasma membrane connection: PtdIns(4, 5)P2 influences cytoskeletal protein activity at the plasma membrane. J. Cell Sci. 113, 3685-3695.
Smilenov, L. B., Mikhailov, A., Pelham, R. J., Marcantonio, E. E. and Gundersen, G. G. (1999). Focal adhesion motility revealed in stationary fibroblasts. Science 286, 1172-1174.
Tang, H., Kerins, D. M., Hao, Q., Inagami, T. and Vaughan, D. E. (1998). The urokinase-type plasminogen activator receptor mediates tyrosine phosphorylation of focal adhesion proteins and activation of mitogen- activated protein kinase in cultured endothelial cells. J. Biol. Chem. 273, 18268-18272.
Tarone, G., Cirillo, D., Giancotti, F. G., Comoglio, P. M. and Marchisio, P. C. (1985). Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes. Exp. Cell Res. 159, 141-157.[Medline]
Turner, C. E., Glenney, J. R., Jr and Burridge, K. (1990). Paxillin: a new vinculin-binding protein present in focal adhesions. J. Cell Biol. 111, 1059-1068.[Abstract]
Volberg, T., Romer, L., Zamir, E. and Geiger, B. (2001). pp60c-src and related tyrosine kinases: a role in the assembly and reorganization of matrix adhesions. J. Cell Sci. 114, 2279-2289.
Wachsstock, D. H., Wilkins, J. A. and Lin, S. (1987). Specific interaction of vinculin with -actinin. Biochem. Biophys. Res. Commun. 146, 554-560.[Medline]
Watanabe, N., Kato, T., Fujita, A., Ishizaki, T. and Narumiya, S. (1999). Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat. Cell Biol. 1, 136-143.[Medline]
Weekes, J., Barry, S. T. and Critchley, D. R. (1996). Acidic phospholipids inhibit the intramolecular association between the N- and C-terminal regions of vinculin, exposing actin-binding and protein kinase C phosphorylation sites. Biochem. J. 314, 827-832.[Medline]
Wei, Y., Yang, X., Liu, Q., Wilkins, J. A. and Chapman, H. A. (1999). A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling. J. Cell Biol. 144, 1285-1294.
Wesolowski, G., Duong, L. T., Lakkakorpi, P. T., Nagy, R. M., Tezuka, K., Tanaka, H., Rodan, G. A. and Rodan, S. B. (1995). Isolation and characterization of highly enriched, prefusion mouse osteoclastic cells. Exp. Cell Res. 219, 679-686.[Medline]
Wilkins, J. A. and Lin, S. (1982). High-affinity interaction of vinculin with actin filaments in vitro. Cell 28, 83-90.[Medline]
Williams, J. C., Weijland, A., Gonfloni, S., Thompson, A., Courtneidge, S. A., Superti-Furga, G. and Wierenga, R. K. (1997). The 2.35 Å crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions. J. Mol. Biol. 274, 757-775.[Medline]
Winkler, J., Lunsdorf, H. and Jockusch, B. M. (1996). The ultrastructure of chicken gizzard vinculin as visualized by high-resolution electron microscopy. J. Struct. Biol. 116, 270-277.[Medline]
Wood, C. K., Turner, C. E., Jackson, P. and Critchley, D. R. (1994). Characterisation of the paxillin-binding site and the C-terminal focal adhesion targeting sequence in vinculin. J. Cell Sci. 107, 709-717.
Woods, A. and Couchman, J. R. (1994). Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component. Mol. Biol. Cell 5, 183-192.[Abstract]
Woods, A. and Couchman, J. R. (1998). Syndecans: synergistic activators of cell adhesion. Trends Cell Biol. 8, 189-192.[Medline]
Woods, A., Longley, R. L., Tumova, S. and Couchman, J. R. (2000). Syndecan-4 binding to the high affinity heparin-binding domain of fibronectin drives focal adhesion formation in fibroblasts. Arch. Biochem. Biophys. 374, 66-72.[Medline]
Wouters, F. S., Bastiaens, P. I., Wirtz, K. W. and Jovin, T. M. (1998). FRET microscopy demonstrates molecular association of non-specific lipid transfer protein (nsL-TP) with fatty acid oxidation enzymes in peroxisomes. EMBO J. 17, 7179-7189.
Xu, W., Harrison, S. C. and Eck, M. J. (1997). Three-dimensional structure of the tyrosine kinase c-Src. Nature 385, 595-602.[Medline]
Yebra, M., Goretzki, L., Pfeifer, M. and Mueller, B. M. (1999). Urokinase-type plasminogen activator binding to its receptor stimulates tumor cell migration by enhancing integrin-mediated signal transduction. Exp. Cell Res. 250, 231-240.[Medline]
Zamir, E. and Geiger, B. (2001). Components of cell-matrix adhesions. J. Cell Sci. 114, 3577-3579.
Zamir, E., Katz, B. Z., Aota, S., Yamada, K. M., Geiger, B. and Kam, Z. (1999). Molecular diversity of cell-matrix adhesions. J. Cell Sci. 112, 1655-1669.
Zamir, E., Katz, M., Posen, Y., Erez, N., Yamada, K. M., Katz, B. Z., Lin, S., Lin, D. C., Bershadsky, A., Kam, Z. et al. (2000). Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat. Cell Biol. 2, 191-196.[Medline]
Zimmermann, P. and David, G. (1999). The syndecans, tuners of transmembrane signaling. FASEB J. 13 Suppl., S91-S100.