v-SRC'S hold over actin and cell adhesions

Hunter, T. & Sefton, B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc. Natl Acad. Sci. USA 77, 1311–1315 (1980).

Martin, G. S. The hunting of the Src. Nature Rev. Mol. Cell Biol. 2, 467–475 (2001).A historical perspective on the landmarks in cancer research provided by the Src proteins.

Kellie, S., Patel, B., Wigglesworth, N. M., Critchley, D. R. & Wyke, J. A. The use of Rous sarcoma virus transformation mutants with differing tyrosine kinase activities to study the relationships between vinculin phosphorylation, pp60v-src location and adhesion plaque integrity. Exp. Cell Res. 165, 216–228 (1986).

David-Pfeuty, T. & Singer, S. J. Altered distributions of the cytoskeletal proteins vinculin and α-actinin in cultured fibroblasts transformed by Rous sarcoma virus. Proc. Natl Acad. Sci. USA 77, 6687–6691 (1980).

Boschek, C. B. et al. Early changes in the distribution and organization of microfilament proteins during cell transformation. Cell 24, 175–184 (1981).

Shriver, K. & Rohrschneider, L. Organization of pp60src and selected cytoskeletal proteins within adhesion plaques and junctions of Rous sarcoma virus-transformed rat cells. J. Cell Biol. 89, 525–535 (1981).

Jove, R. & Hanafusa, H. Cell transformation by the viral src oncogene. Annu. Rev. Cell Biol. 3, 31–56 (1987).

Hanafusa, H. Cell Transformation by RNA Tumour Viruses (ed. Fraenkel-Conrat, H. & Wagner, R. R.) (Plenum Publishing, New York, 1977).

Hynes, R. Phosphorylation of vinculin by pp60src: what might it mean? Cell 28, 437–438 (1982).

Kellie, S. et al. Membrane and cytoskeletal changes in cells after transformation by Rous sarcoma virus. Biochem. Soc. Trans. 15, 791–794 (1987).

Rohrschneider, L. & Rosok, M. J. Transformation parameters and pp60src localization in cells infected with partial transformation mutants of Rous sarcoma virus. Mol. Cell Biol. 3, 731–746 (1983).

Courtneidge, S. A. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation. EMBO J. 4, 1471–1477 (1985).This work showed that binding of SV40 middle T, and reduced tyrosine phosphorylation, were associated with enhanced c-Src-kinase activity.

Cooper, J. A., Gould, K. L., Cartwright, C. A. & Hunter, T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science 231, 1431–1434 (1986).This work established that regulatory phosphorylation of tyrosine 527 at the carboxyl terminus of c-Src negatively influenced enzymatic activity. This was particularly interesting because this residue was missing from v-Src — as carboxy-terminal sequences were replaced by alternative amino acids — and rendered v-Src refractory to this negative regulation.

Thomas, S. M. & Brugge, J. S. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Dev. Biol. 13, 513–609 (1997).

Willingham, M. C., Jay, G. & Pastan, I. Localization of the ASV src gene product to the plasma membrane of transformed cells by electron microscopic immunocytochemistry. Cell 18, 125–134 (1979).

Rohrschneider, L. R. Immunofluorescence on avian sarcoma virus-transformed cells: localization of the src gene product. Cell 16, 11–24 (1979).

Courtneidge, S. A., Levinson, A. D. & Bishop, J. M. The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and a homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane. Proc. Natl Acad. Sci. USA 77, 3783–3787 (1980).

Krueger, J. G., Garber, E. A., Chin, S. S., Hanafusa, H. & Goldberg, A. R. Size-variant pp60src proteins of recovered avian sarcoma viruses interact with adhesion plaques as peripheral membrane proteins: effects on cell transformation. Mol. Cell. Biol. 4, 454–467 (1984).

Nigg, E. A., Sefton, B. M., Hunter, T., Walter, G. & Singer, S. J. Immunofluorescent localization of the transforming protein of Rous sarcoma virus with antibodies against a synthetic src peptide. Proc. Natl Acad. Sci. USA 79, 5322–5326 (1982).

Welham, M. J. & Wyke, J. A. A single point mutation has pleiotropic effects on pp60v-src function. J. Virol. 62, 1898–1906 (1988).

Fincham, V. J. et al. Translocation of Src kinase to the cell periphery is mediated by the actin cytoskeleton under the control of the Rho family of small G proteins. J. Cell Biol. 135, 1551–1564 (1996).This paper showed for the first time that v-Src's peripheral targeting was controlled by actin modelling, through the Rho family of small G-proteins.

Fincham, V. J., Brunton, V. G. & Frame, M. C. The SH3 domain directs acto-myosin-dependent targeting of v-Src to focal adhesions via phosphatidylinositol 3-kinase. Mol. Cell. Biol. 20, 6518–6536 (2000).

Fincham, V. J. & Frame, M. C. The catalytic activity of Src is dispensable for translocation to focal adhesions but controls the turnover of these structures during cell motility. EMBO J. 17, 81–92 (1998).

Erpel, T., Superti-Furga, G. & Courtneidge, S. A. Mutational analysis of the Src SH3 domain: the same residues of the ligand binding surface are important for intra- and intermolecular interactions. EMBO J. 14, 963–975 (1995).

Wages, D. S., Keefer, J., Rall, T. B. & Weber, M. J. Mutations in the SH3 domain of the src oncogene which decrease association of phosphatidylinositol 3′-kinase activity with pp60v-src and alter cellular morphology. J. Virol. 66, 1866–1874 (1992).These workers were the first to show that SH3-domain mutations suppressed PI3K binding to v-Src, and that this, in turn, was associated with weak transformation.

Brugge, J. S. Interaction of the Rous sarcoma virus protein pp60src with the cellular proteins pp50 and pp90. Curr. Top. Microbiol. Immunol. 123, 1–22 (1986).

Hauck, C. R., Hsia, D. A., Ilic, D. & Schlaepfer, D. D. v-Src SH3-enhanced interaction with focal adhesion kinase at β1 integrin–containing invadopodia promotes cell invasion. J. Biol. Chem. 2002 Feb 11; [epub ahead of print].

Kaplan, K. B., Swedlow, J. R., Varmus, H. E. & Morgan, D. O. Association of p60c-src with endosomal membranes in mammalian fibroblasts. J. Cell Biol. 118, 321–333 (1992).

Kaplan, K. B. et al. Association of the amino-terminal half of c-Src with focal adhesions alters their properties and is regulated by phosphorylation of tyrosine 527. EMBO J. 13, 4745–4756 (1994).

Timpson, P., Jones, G. E., Frame, M. C. & Brunton, V. G. Co-ordination of cell polarisation and migration by the Rho family GTPases requires Src tyrosine kinase. Curr. Biol. 11, 1836–1846 (2001).

Courtneidge, S. A. Transformation by polyoma virus middle T antigen. Cancer Surv. 5, 173–182 (1986).

Schu, P. V. et al. Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science 260, 88–91 (1993).

Brown, M. T. et al. ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src. Mol. Cell. Biol. 18, 7038–7051 (1998).

Randazzo, P. A. et al. The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proc. Natl Acad. Sci. USA 97, 4011–4016 (2000).

Gillham, H., Golding, M. C., Pepperkok, R. & Gullick, W. J. Intracellular movement of green fluorescent protein-tagged phosphatidylinositol 3-kinase in response to growth factor receptor signaling. J. Cell Biol. 146, 869–880 (1999).

Fincham, V. J., James, M., Frame, M. C. & Winder, S. J. Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBO J. 19, 2911–2923 (2000).

Brunton, V. G. et al. The protrusive phase and full development of integrin-dependent adhesions in colon epithelial cells require FAK- and ERK-mediated actin spike formation: deregulation in cancer cells. Neoplasia 3, 215–226 (2001).

Turner, C. E. Paxillin interactions. J. Cell Sci. 113, 4139–4140 (2000).

Ku, H. & Meier, K. E. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells. J. Biol. Chem. 275, 11333–11340 (2000).

Aplin, A. E. & Juliano, R. L. Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton. J. Cell Biol. 155, 187–192 (2001).

Aplin, A. E., Stewart, S. A., Assoian, R. K. & Juliano, R. L. Integrin-mediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1. J. Cell Biol. 153, 273–282 (2001).

Tarone, G., Cirillo, D., Giancotti, F. G., Comoglio, P. M. & Marchisio, P. C. Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes. Exp. Cell Res. 159, 141–157 (1985).

Mizutani, K., Miki, H., He, H., Maruta, H. & Takenawa, T. Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts. Cancer Res. 62, 669–674 (2002).

Wu, H. & Parsons, J. T. Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex. J. Cell Biol. 120, 1417–1426 (1993).

Weed, S. A., Du, Y. & Parsons, J. T. Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1. J. Cell Sci. 111, 2433–2443 (1998).

Hiura, K., Lim, S. S., Little, S. P., Lin, S. & Sato, M. Differentiation dependent expression of tensin and cortactin in chicken osteoclasts. Cell. Motil. Cytoskeleton 30, 272–284 (1995).

Huang, C. et al. Down-regulation of the filamentous actin cross-linking activity of cortactin by Src-mediated tyrosine phosphorylation. J. Biol. Chem. 272, 13911–13915 (1997).

Weed, S. A. et al. Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex. J. Cell Biol. 151, 29–40 (2000).

Weaver, A. M. et al. Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr. Biol. 11, 370–374 (2001).This showed that cortactin stabilizes newly generated filament branch points through effects on Arp2, and that cortactin therefore promotes the formation and stabilization of the actin network that may drive protrusion at the leading edge of migrating cells.

Flynn, D. C., Leu, T. H., Reynolds, A. B. & Parsons, J. T. Identification and sequence analysis of cDNAs encoding a 110-kilodalton actin filament-associated pp60src substrate. Mol. Cell. Biol. 13, 7892–7900 (1993).

Klinghoffer, R. A., Sachsenmaier, C., Cooper, J. A. & Soriano, P. Src family kinases are required for integrin but not PDGFR signal transduction. EMBO J. 18, 2459–2471 (1999).The triple knockout of Src, Fyn and Yes showed that the Src family kinases have an important role in integrin-dependent cell migration.

Felsenfeld, D. P., Schwartzberg, P. L., Venegas, A., Tse, R. & Sheetz, M. P. Selective regulation of integrin–cytoskeleton interactions by the tyrosine kinase Src. Nature Cell Biol. 1, 200–206 (1999).

Ilic, D. et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544 (1995).This work showed that cells that were derived from FAK-deficient mouse embryos also showed impaired motility.

Zou, J. X., Liu, Y., Pasquale, E. B. & Ruoslahti, E. Activated SRC oncogene phosphorylates R-ras and suppresses integrin activity. J. Biol. Chem. 277, 1824–1827 (2002).

Ellis, C., Moran, M., McCormick, F. & Pawson, T. Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases. Nature 343, 377–381 (1990).

Settleman, J., Albright, C. F., Foster, L. C. & Weinberg, R. A. Association between GTPase activators for Rho and Ras families. Nature 359, 153–154 (1992).

Settleman, J., Narasimhan, V., Foster, L. C. & Weinberg, R. A. Molecular cloning of cDNAs encoding the GAP-associated protein p190: implications for a signaling pathway from ras to the nucleus. Cell 69, 539–549 (1992).

Ridley, A. J. et al. rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. EMBO J. 12, 5151–5160 (1993).

McGlade, J. et al. The amino-terminal region of GAP regulates cytoskeletal structure and cell adhesion. EMBO J. 12, 3073–3081 (1993).

Fincham, V. J., Chudleigh, A. & Frame, M. C. Regulation of p190 Rho-GAP by v-Src is linked to cytoskeletal disruption during transformation. J. Cell Sci. 112, 947–956 (1999).

Mayer, T., Meyer, M., Janning, A., Schiedel, A. C. & Barnekow, A. A mutant form of the rho protein can restore stress fibers and adhesion plaques in v-src transformed fibroblasts. Oncogene 18, 2117–2128 (1999).

Arthur, W. T., Petch, L. A. & Burridge, K. Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. Curr. Biol. 10, 719–722 (2000).This paper showed that integrin engagement can suppress RhoA activity, perhaps by c-Src-induced phosphorylation of p190 RhoGAP, that could lead to transient relaxing of contractile forces that are necessary for protrusion at the leading edges of migrating cells.

Arthur, W. T. & Burridge, K. RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity. Mol. Biol. Cell 12, 2711–2720 (2001).

Belsches, A. P., Haskell, M. D. & Parsons, S. J. Role of c-Src tyrosine kinase in EGF-induced mitogenesis. Front Biosci. 2, D501–D518 (1997).

Roof, R. W. et al. Phosphotyrosine (p-Tyr)-dependent and -independent mechanisms of p190 RhoGAP–p120 RasGAP interaction: Tyr 1105 of p190, a substrate for c-Src, is the sole p-Tyr mediator of complex formation. Mol. Cell. Biol. 18, 7052–7063 (1998).

Brouns, M. R., Matheson, S. F. & Settleman, J. p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation. Nature Cell Biol. 3, 361–367 (2001).

Felice, G. R., Eason, P., Nermut, M. V. & Kellie, S. pp60v-src association with the cytoskeleton induces actin reorganization without affecting polymerization status. Eur. J. Cell Biol. 52, 47–59 (1990).

Billuart, P., Winter, C. G., Maresh, A., Zhao, X. & Luo, L. Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway. Cell 107, 195–207 (2001).

Fincham, V. J., Wyke, J. A. & Frame, M. C. v-Src-induced degradation of focal adhesion kinase during morphological transformation of chicken embryo fibroblasts. Oncogene 10, 2247–2252 (1995).

McLean, G. W., Fincham, V. J. & Frame, M. C. v-Src induces tyrosine phosphorylation of focal adhesion kinase independently of tyrosine 397 and formation of a complex with Src. J. Biol. Chem. 275, 23333–23339 (2000).

Sorimachi, H., Saido, T. C. & Suzuki, K. New era of calpain research. Discovery of tissue-specific calpains. FEBS Lett. 343, 1–5 (1994).

Molinari, M. & Carafoli, E. Calpain: a cytosolic proteinase active at the membranes. J. Membr. Biol. 156, 1–8 (1997).

Kawasaki, H., Emori, Y., Imajoh-Ohmi, S., Minami, Y. & Suzuki, K. Identification and characterization of inhibitory sequences in four repeating domains of the endogenous inhibitor for calcium-dependent protease. J. Biochem. (Tokyo) 106, 274–281 (1989).

Croall, D. E. & DeMartino, G. N. Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol. Rev. 71, 813–847 (1991).

Dourdin, N. et al. Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts. J. Biol. Chem. 276, 48382–48388 (2001).

Huttenlocher, A. et al. Regulation of cell migration by the calcium-dependent protease calpain. J. Biol. Chem. 272, 32719–32722 (1997).Data shown here indicate that calpain inhibition modulates cell migration by stabilizing cytoskeletal/adhesive links and decreasing the rate of retraction at the trailing edge of the cell.

Palecek, S. P., Huttenlocher, A., Horwitz, A. F. & Lauffenburger, D. A. Physical and biochemical regulation of integrin release during rear detachment of migrating cells. J. Cell Sci. 111, 929–940 (1998).

Beckerle, M. C., Burridge, K., DeMartino, G. N. & Croall, D. E. Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion. Cell 51, 569–577 (1987).

Selliah, N., Brooks, W. H. & Roszman, T. L. Proteolytic cleavage of α-actinin by calpain in T cells stimulated with anti-CD3 monoclonal antibody. J. Immunol. 156, 3215–3221 (1996).

Hayashi, M., Suzuki, H., Kawashima, S., Saido, T. C. & Inomata, M. The behavior of calpain-generated amino- and carboxy-terminal fragments of talin in integrin-mediated signaling pathways. Arch. Biochem. Biophys. 371, 133–141 (1999).

Yamaguchi, R., Maki, M., Hatanaka, M. & Sabe, H. Unphosphorylated and tyrosine-phosphorylated forms of a focal adhesion protein, paxillin, are substrates for calpain II in vitro: implications for the possible involvement of calpain II in mitosis-specific degradation of paxillin. FEBS Lett. 356, 114–116 (1994).

Oda, A., Druker, B. J., Ariyoshi, H., Smith, M. & Salzman, E. W. pp60src is an endogenous substrate for calpain in human blood platelets. J. Biol. Chem. 268, 12603–12608 (1993).

Cooray, P. et al. Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain. Biochem. J. 318, 41–47 (1996).

Glading, A., Lauffenburger, D. A. & Wells, A. Cutting to the chase: calpain proteases in cell motility. Trends Cell Biol. 12, 46–54 (2002).

Carragher, N. O., Fincham, V. J., Riley, D. & Frame, M. C. Cleavage of focal adhesion kinase by different proteases during SRC-regulated transformation and apoptosis. Distinct roles for calpain and caspases. J. Biol. Chem. 276, 4270–4275 (2001).

Carragher, N. O. et al. v-Src induced modulation of the calpain–calpastatin proteolytic system regulates transformation. Mol. Cell. Biol. 22, 257–269 (2002).This work shows that v-Src activity modulates calpain activity, and leads to proteolysis of focal adhesion kinase during transformation. V-Src-induced, calpain-mediated proteolysis is also required for anchorage-independent growth.

Carragher, N. O., Levkau, B., Ross, R. & Raines, E. W. Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin. J. Cell Biol. 147, 619–630 (1999).

Xie, H. et al. EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCγ signaling pathway. J. Cell Sci. 111, 615–624 (1998).

Welsh, J. B., Gill, G. N., Rosenfeld, M. G. & Wells, A. A negative feedback loop attenuates EGF-induced morphological changes. J. Cell Biol. 114, 533–543 (1991).

Fujio, Y., Yamada, F., Takahashi, K. & Shibata, N. Altered fibronectin-dependent cell adhesion by PDGF accompanies phenotypic modulation of vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 196, 997–1002 (1993).

Glading, A., Uberall, F., Keyse, S. M., Lauffenburger, D. A. & Wells, A. Membrane proximal ERK signaling is required for M-calpain activation downstream of epidermal growth factor receptor signaling. J. Biol. Chem. 276, 23341–23348 (2001).

Sieg, D. J. et al. FAK integrates growth-factor and integrin signals to promote cell migration. Nature Cell Biol. 2, 249–256 (2000).

Roche, S., Koegl, M., Barone, M. V., Roussel, M. F. & Courtneidge, S. A. DNA synthesis induced by some but not all growth factors requires Src family protein tyrosine kinases. Mol. Cell. Biol. 15, 1102–1109 (1995).This paper showed the requirement for Src family kinase activity during growth factor-induced mitogenesis.

Rodier, J. M., Valles, A. M., Denoyelle, M., Thiery, J. P. & Boyer, B. pp60c-src is a positive regulator of growth factor-induced cell scattering in a rat bladder carcinoma cell line. J. Cell Biol. 131, 761–773 (1995).

Maa, M. C., Leu, T. H., McCarley, D. J., Schatzman, R. C. & Parsons, S. J. Potentiation of epidermal growth factor receptor-mediated oncogenesis by c-Src: implications for the etiology of multiple human cancers. Proc. Natl Acad. Sci. USA 92, 6981–6985 (1995).

Luttrell, D. K., Luttrell, L. M. & Parsons, S. J. Augmented mitogenic responsiveness to epidermal growth factor in murine fibroblasts that overexpress pp60c-src. Mol. Cell. Biol. 8, 497–501 (1988).

Patel, Y. M. & Lane, M. D. Mitotic clonal expansion during preadipocyte differentiation: calpain-mediated turnover of p27. J. Biol. Chem. 275, 17653–17660 (2000).

Riley, D., Carragher, N. O., Frame, M. C. & Wyke, J. A. The mechanism of cell cycle regulation by v-Src. Oncogene 20, 5941–5950 (2001).

Abram, C. L. & Courtneidge, S. A. Src family tyrosine kinases and growth factor signaling. Exp. Cell Res. 254, 1–13 (2000).

Takeda, H. et al. v-src kinase shifts the cadherin-based cell adhesion from the strong to the weak state and β-catenin is not required for the shift. J. Cell Biol. 131, 1839–1847 (1995).

Hamaguchi, M. et al. p60v-src causes tyrosine phosphorylation and inactivation of the amino-cadherin–catenin cell adhesion system. EMBO J. 12, 307–314 (1993).

Matsuyoshi, N. et al. Cadherin-mediated cell–cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J. Cell Biol. 118, 703–714 (1992).

Behrens, J. et al. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/β-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J. Cell Biol. 120, 757–766 (1993).

Fujita, Y. et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nature Cell Biol. 4, 222–231 (2002).This important recent work identified a new Src-regulated protein, termed Hakai, that ubiquitylates and induces endocytosis of the E-cadherin complex. This might provide a mechanism whereby elevated Src in tumours can destabilize cadherin-mediated adhesions.

Kinch, M. S., Clark, G. J., Der, C. J. & Burridge, K. Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia. J. Cell Biol. 130, 461–471 (1995).

Sato, C., Tsuboi, R., Shi, C. M., Rubin, J. S. & Ogawa, H. Comparative study of hepatocyte growth factor/scatter factor and keratinocyte growth factor effects on human keratinocytes. J. Invest. Dermatol. 104, 958–963 (1995).

Shibamoto, S. et al. Tyrosine phosphorylation of β-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes. Commun. 1, 295–305 (1994).

Boyer, B., Roche, S., Denoyelle, M. & Thiery, J. P. Src and Ras are involved in separate pathways in epithelial cell scattering. EMBO J. 16, 5904–5913 (1997).

Calautti, E. et al. Tyrosine phosphorylation and src family kinases control keratinocyte cell–cell adhesion. J. Cell Biol. 141, 1449–1465 (1998).

Owens, D. W. et al. The catalytic activity of the Src family kinases is required to disrupt cadherin-dependent cell–cell contacts. Mol. Biol. Cell 11, 51–64 (2000).

Covault, J., Liu, Q. Y. & El-Deeb, S. Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin. Brain Res. Mol. Brain Res. 11, 11–16 (1991).

Sato, N. et al. Elevated calcium level induces calcium-dependent proteolysis of A-CAM (N-cadherin) in heart-analysis by detergent-treated model. Biochem. Biophys. Res. Commun. 217, 649–653 (1995).

Tominaga, T. et al. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Mol. Cell 5, 13–25 (2000).

Wyke, J. A. The selective isolation of temperature-sensitive mutants of Rous sarcoma virus. Virology 52, 587–590 (1973).

Catling, A. D., Wyke, J. A. & Frame, M. C. Mitogenesis of quiescent chick fibroblasts by v-Src: dependence on events at the membrane leading to early changes in AP-1. Oncogene 8, 1875–1886 (1993).

Sorimachi, H. & Suzuki, K. The structure of calpain. J. Biochem. (Tokyo) 129, 653–664 (2001).

Mellgren, R. L., Lane, R. D. & Mericle, M. T. The binding of large calpastatin to biologic membranes is mediated in part by interaction of an amino terminal region with acidic phospholipids. Biochim. Biophys. Acta 999, 71–77 (1989).

Lee, W. J. et al. Molecular diversity in amino-terminal domains of human calpastatin by exon skipping. J. Biol. Chem. 267, 8437–8442 (1992).

Lu, Z., Jiang, G., Blume-Jensen, P. & Hunter, T. Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase. Mol. Cell. Biol. 21, 4016–4031 (2001).