Focal adhesion kinase in integrin-mediated signaling

Cary, Leslie A.; Guan, Jun‐Lin

doi:10.2741/cary

Cited by 325 publications

(244 citation statements)

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“…The site of convergence of these adhesive receptors initiates FAK recruitment and activation, leading to the formation of a mature focal adhesion. 24 In this study, we find that the association between CIB and FAK occurs only on cell attachment to Fg ( Figure 7A). In fact, as noted in Figure 7A, filopodia that do not contact Fg fail to exhibit FAK staining, and, hence, CIB and FAK colocalization is not observed.…”

mentioning

confidence: 85%

“…We chose CHO cells as our mammalian expression model, as these cells have been widely used as a simplified model to study platelet-related events, [21][22][23][24][25][26] and thus overexpressed recombinant human CIB in CHO cells to better understand its physiologic role. Although CHO cells are not of human origin, the fact that CIB is so highly conserved among species ( Figure 1A) suggests that overexpression of human CIB may complement the endogenous signaling.…”

Section: Overexpression Of Cib Induces Cell Migrationmentioning

confidence: 99%

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Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen

Naik

2003

Blood

106

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IntroductionPlatelet adhesion to and spreading on the subendothelial matrix is integral to the maintenance of physiologic hemostasis and thrombosis. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the platelet fibrinogen (Fg) receptor, which mediates both platelet aggregation and platelet spreading on vascular matrices at sites of vascular injury. [1][2][3][4][5] However, the exact signaling mechanism that takes place on GPIIb/IIIa binding to immobilized Fg that leads to platelet spreading, broadly classified as outside-in signaling, has only been partially defined.The nonreceptor tyrosine kinases Syk and Src were shown to be involved in this signaling cascade. 4,[6][7][8] On activation of Syk, Src, and possibly a number of other kinases as a result of GPIIb/IIIa binding to Fg, discoid platelets undergo a rapid shape change during which adherent platelets transiently exhibit filopodia-like structures. This fleeting event involves rapid actin depolymerization and repolymerization events, resulting in a spiky morphology. Dynamic reorganization of the platelet cytoskeleton triggers a signaling cascade that results in secretion of platelet agonists such as adenosine diphosphate (ADP) and serotonin from platelet dense granules and adhesive proteins such as platelet factor 4, Fg, and von Willebrand factor from ␣-granules. 9 Binding of agonists to their receptors initiates extensive signaling events that lead to a second wave of cytoskeletal reorganization and culminate in a fully spread platelet morphology. However, the signaling events required to achieve each of these distinct morphologies have not yet been clearly elucidated.Recently, we have reported that the interaction between calcium and integrin binding protein (CIB) and GPIIb/IIIa is required for the process of platelet spreading on immobilized Fg. 10 We find that, on ligand binding, most CIB binds to GPIIb/IIIa to form a complex. Inhibition of complex formation by introduction of either anti-CIB antibody or GPIIb cytoplasmic tail peptide into platelets blocks platelet spreading but not adhesion or filopodia formation. However, a spread morphology can be recovered by the introduction of recombinant CIB into antibody-or GPIIb peptide-inhibited platelets. The identity of the signaling components downstream of CIB in this process is not yet known.In this report, we identify focal adhesion kinase (FAK) as a downstream component of CIB-induced signaling. FAK activation has been shown to require actin polymerization events, implicating its role in the second wave of cytoskeletal rearrangement. 11,12 In fact, it has been shown that secretion of ADP controls activation of both FAK and phosphatidylinositol 3-kinase (PI3K), 13,14 which is essential for platelet spreading. To determine the downstream effects of CIB signaling that lead to platelet spreading without the complications from signaling events because of secretion, we reconstituted CIB-mediated signaling in Chinese hamster ovary (CHO) cells. We find that overexpression of CIB in CHO cells induces migration, a process wh...

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confidence: 85%

Section: Overexpression Of Cib Induces Cell Migrationmentioning

confidence: 99%

Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen

Naik

2003

Blood

106

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“…A recent historical review gives the perspective and nomenclature in the field of signal transduction (Hunter, 2000) and may be another possible starting point. Several good review articles on the pathways of interest (Mecham, 1991;Meredith et al, 1996;Cary and Guan, 1999;Gonzalez-Amaro and SanchezMadrid, 1999;Duong et al, 2000;Ridley, 2000a,b;Roovers and Assoian, 2000) combined with a few colleagues or students are the ingredients needed to start a journal club. The journal club should start by reading the chapters in a modern cell biology text (Lodish et al, 2000), or a monograph on the specific subject, followed by some review articles, then tackle at least one current article a week.…”

Section: Getting Startedmentioning

confidence: 99%

“…An example of this type of protein was discussed previously in describing the integrin molecules; focal adhesion kinase (FAK) becomes phosphorylated when integrins bind to their ligand, ECM. Once FAK becomes phosphorylated, it will activate or phosphorylate paxillin, an actin-associated protein, and another kinase, Src (Cary and Guan, 1999). Src can also start activating surrounding proteins, creating an amplification of the original signal.…”

Section: Intracellular Signaling Proteinsmentioning

confidence: 99%

Approaches to studying cellular signaling: A primer for morphologists

Svoboda¹,

Reenstra²

2002

Anat. Rec.

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Many research projects will lead to understanding tissue and/or cell responses to extracellular influences either from soluble factors or the surrounding extracellular matrix. These types of investigations will require the understanding of signal transduction. This particular cell biological field has literally exploded with information and new technical approaches in the past 10 years. This article is directed toward investigators interested in using these new approaches to study their systems. An overview of the general principles of signal transduction events including the types of receptors and intracellular signaling events is followed by an introduction to methods for visualizing signal transduction. This is followed by an introduction to biochemical analysis and an example of combining several approaches to understanding a tissue response to extracellular matrix stimulus. Anat Rec (New Anat) 269: 123-139, 2002.

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“…p130 CAS and paxillin are both Src substrates and bind to FAK with their SH3 domains (23). The adaptor protein Crk, which was first discovered as a highly tyrosine-phosphorylated protein in Rous sarcoma-transformed cells (24), forms a complex with tyrosinephosphorylated p130 CAS (25).…”

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confidence: 99%

The Integrin α7 Cytoplasmic Domain Regulates Cell Migration, Lamellipodia Formation, and p130CAS/Crk Coupling

Mielenz¹,

Hapke

Pöschl

et al. 2001

Journal of Biological Chemistry

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The integrin ␣ 7 ␤ 1 is the major laminin-binding integrin in skeletal, heart, and smooth muscle and is a receptor for laminin-1 and -2. It mediates myoblast migration on laminin-1 and -2 and thus might be involved in muscle development and repair. Previously we have shown that ␣ 7 B as well as the ␣ 7 A and -C splice variants induce cell motility on laminin when transfected into nonmotile HEK293 cells. In this study we have investigated the role of the cytoplasmic domain of ␣ 7 in the laminin-induced signal transduction of ␣ 7 ␤ 1 integrin regulating cell adhesion and migration. Deletion of the cytoplasmic domain did not affect assembly of the mutated ␣ 7 ⌬cyt/␤ 1 heterodimer on the cell surface or adhesion of ␣ 7 ⌬cyt-transfected cells to laminin. The motility of these cells on the laminin-1/E8 fragment, however, was significantly reduced to the level of mock-transfected cells; lamellipodia formation and polarization of the cells were also impaired. Adhesion to the laminin-1/E8 fragment induced tyrosine phosphorylation of the focal adhesion kinase, paxillin, and p130 CAS as well as the formation of a p130 CAS -Crk complex in wild-type ␣ 7 B-transfected cells. In ␣ 7 B⌬cyt cells, however, the extent of p130 CAS tyrosine formation was reduced and formation of the p130 CAS -Crk complex was impaired, with unaltered levels of p130 CAS and Crk protein levels. These findings indicate adhesion-dependent regulation of p130 CAS /Crk complex formation by the cytoplasmic domain of ␣ 7 B integrin after cell adhesion to laminin-1/E8 and imply ␣ 7 B-controlled lamellipodia formation and cell migration through the p130 CAS /Crk protein complex.During muscle repair, undifferentiated muscle precursor cells, so-called satellite cells, are activated and migrate to sites of damaged muscle along the basement membranes of preexisting muscle fibers to close the wound by proliferating and fusing (1, 2). In vitro, skeletal myoblasts have been shown to migrate on laminin (LN) 1 1 (3), the laminin-1-E8 fragment that is derived from laminin-1 by elastase digestion (4), and on laminin-2 (5), but not on fibronectin (4). The major component of muscle basement membranes supporting muscle cell migration is laminin-2 (6). The migration of fibroblast-like cells in culture involves polarization of cells, formation of filopodia, lamellipodia, stress fibers, and myosin-based contractility (7). Filopodia, lamellipodia and stress fiber formation are mediated by Cdc42, Rac, and Rho, respectively, which are members of the Rho family of small GTPases (8). Cdc42, Rac, and Rho can either be activated by soluble factors like growth factors, bioactive peptides, and hormones (8) or by integrins (9, 10), which can transduce signals from the extracellular matrix after clustering and ligand-induced conformational changes (11) in a hierarchical fashion (12). Several proteins become tyrosine-phosphorylated after integrin-mediated cell attachment. Those are, among others, the focal adhesion kinase (FAK) (13), the adaptor protein p130 CAS (Crk-associated Src substr...

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Focal adhesion kinase in integrin-mediated signaling

Cited by 325 publications

References 132 publications

Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen

Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen

Approaches to studying cellular signaling: A primer for morphologists

The Integrin α7 Cytoplasmic Domain Regulates Cell Migration, Lamellipodia Formation, and p130CAS/Crk Coupling

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