Multiple connections link FAK to cell motility and invasion

Schlaepfer, David D.; Mitra, Satyajit K.

doi:10.1016/j.gde.2003.12.002

Cited by 374 publications

(329 citation statements)

References 66 publications

Supporting

Mentioning

308

Contrasting

Unclassified

Order By: Relevance

“…Likely, the effects of focal adhesion signaling and GPCR signaling on ERK activation are additive in the in vivo setting of labor as illustrated in Figure 6. In this model, consistent with the results presented here, stretch-induced integrin clustering can lead to FAK phosphorylation [Schlaepfer and Mitra, 2004], creating docking sites for Src and paxillin. Furthermore, activated Src facilitates the maximal FAK activation through further phosphorylation of FAK [Schlaepfer and Mitra, 2004].…”

Section: Discussionsupporting

confidence: 90%

“…Similarly, integrin engagement and v-Src involvement have been demonstrated in non-muscle cells such as rat embryo fibroblasts to promote cell motility [Fincham et al, 2000]. Integrin engagement in non-muscle cells is known to lead to the activation of a variety of intracellular signaling events via recruitment of signaling molecules to focal adhesion sites [Schlaepfer and Mitra, 2004].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor

Gallant

Malek

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

In late pregnancy rapidly increasing fetal growth dramatically increases uterine wall tension. This process has been implicated in the activation of the myometrium for labor, but the mechanisms involved are unclear. Here, we tested, using a rat model, the hypothesis that gestation-dependent stretch, via activation of focal adhesion signaling, contributes to the published activation of myometrial ERK at the end of pregnancy. Consistent with this hypothesis, we show here that ERK is targeted to adhesion plaques during late pregnancy. Furthermore, myometrial stretch triggers a dramatic increase in myometrial contractility and ERK and caldesmon phosphorylation, confirming the presence of stretch sensitive myometrial signaling element. Screening by anti-phosphotyrosine immunoblotting for focal adhesion signaling in response to stretch reveals a significant increase in the tyrosine phosphorylated bands identified as focal adhesion kinase (FAK), A-Raf, paxillin, and Src. Pretreatment with PP2, a Src inhibitor, significantly suppresses the stretch-induced increases in FAK, paxillin, Src, ERK and caldesmon phosphorylation and myometrial contractility. Thus, focal adhesionSrc signaling contributes to ERK activation and promotes contraction in late pregnancy. These results point to focal adhesion signaling molecules as potential targets in the modulation of the myometrial contractility and the onset of labor.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor

Gallant

Malek

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Kragtorp and Miller (2006) have found that inhibition of Ena/ VASP or FAK leads to abnormal somite rotation and failure to form intersomitic boundaries. Ena/VASP proteins appear to act as a molecular link between cell-surface integrins and the actin cytoskeleton to orchestrate changes in adhesive strength and cell motility (Schlaepfer and Mitra, 2004). Another potential mechanism by which these proteins might regulate cell motility is through activation of integrin adhesion and fibronectin matrix assembly (Kragtorp and Miller, 2006).…”

Section: Local Quantitative Framework Of the Somite Microenvironmentmentioning

confidence: 99%

From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworks

Kulesa

Schnell

Rudloff

et al. 2007

Developmental Dynamics

View full text Add to dashboard Cite

One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short-and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization.

show abstract

“…8 FAK also regulates the cycle of focal contact formation and disassembly required for efficient cell movement and thus, mucosal restitution. 9 Levels of FAK protein expression and/or activation have been correlated to phenotypic changes that affect cell differentiation and function, notably adhesion and migration, in a number of tissues. 10 -13 Targeted FAK deletion in vascular endothelial cells leads to apoptosis and aberrant cell movement whereas FAK overexpression results in increased angiogenesis.…”

mentioning

confidence: 99%

Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

Walsh

Ampasala

Hatfield

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) regulates cell migration, proliferation, and apoptosis. FAK protein is reduced at the edge of migrating gut epithelial sheets in vitro, but it has not been characterized in restitutive gut mucosa in vivo. Here we show that FAK and activated phospho-FAK (FAK 397 ) immunoreactivity was lower in epithelial cells immediately adjacent to human gastric and colonic ulcers in vivo, but dramatically increased in epithelia near the ulcers, possibly reflecting stimulation by growth factors absent in vitro. Transforming growth factor (TGF)-␤, but not fibroblast growth factor, platelet-derived growth factor, or vascular endothelial growth factor, increased FAK levels in Caco-2 and IEC-6 cells. Epithelial immunoreactivity to TGF-␤ and phospho-Smad3 was also higher near the ulcers, varying in parallel with FAK. The TGF-␤ receptor antagonist SB431542 completely blocked TGF-␤-induced Smad2/3 and p38 activation in IEC-6 cells. SB431542 , the p38 antagonist SB203580 , and siRNA-mediated reduction of Smad2 and p38␣ prevented TGF-␤ stimulation of both FAK transcription and translation (as measured via a FAK promoter-luciferase construct). Survival and function of epithelial cells depends critically on interactions between the extracellular matrix and cell surface integrins. These interactions are mediated through focal adhesions, multicomponent juxtamembrane structures that lie at the convergence of integrin adhesion, signaling, and the cytoskeleton.1 Focal adhesion kinase (FAK) is an important nonreceptor tyrosine kinase within the focal adhesion complex.2 Originally described as being rapidly tyrosine phosphorylated on integrin-mediated cell-matrix adhesion, FAK is now known to be activated during epithelial cell motility and phosphorylated at both serine and tyrosine residues by various factors.3-5 Once localized to sites of transmembrane integrin receptor clustering, tyrosine-phosphorylated FAK plays a central role in signal transduction triggered by diverse extracellular signals 6 and represents a convergent point for synergistic interaction between signal pathways activated by growth factors and integrins.7 FAK binds to different signaling proteins via Src homology 2 (SH2) and SH3 recognition sites, acting as a scaffold and transmitting signals crucial to cell survival, motility, proliferation, and differentiation.8 FAK also regulates the cycle of focal contact formation and disassembly required for efficient cell movement and thus, mucosal restitution. 9Levels of FAK protein expression and/or activation have been correlated to phenotypic changes that affect cell differentiation and function, notably adhesion and migration, in a number of tissues. 10 -13 Targeted FAK deletion in vascular endothelial cells leads to apoptosis and aberrant cell movement whereas FAK overexpression results in increased angiogenesis.14,15 Total and activated FAK levels are also directly related to the state of differentiation in human colon cancer. 16 Induction of differentiation in dedifferentiated, rounded, detached Co...

show abstract

Multiple connections link FAK to cell motility and invasion

Cited by 374 publications

References 66 publications

Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor

Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor

From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworks

Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

Contact Info

Product

Resources

About