Organization and post-transcriptional processing of focal adhesion kinase gene

Corsi, Jean-Marc; Rouer, Évelyne; Girault, Jean‐Antoine; Enslen, Hervé

doi:10.1186/1471-2164-7-198

Cited by 72 publications

(72 citation statements)

References 88 publications

(134 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although very few bona fide substrates of FAK have been characterized in intact cells (1), the respective role of FAK catalytic activity and scaffolding properties will have to be determined in these autophosphorylation-independent functions. Autophosphorylation-independent function of FAK is also supported by the observation that although Tyr-397 is highly conserved in most metazoans, it is not found in Caenorhabditis elegans (21).…”

Section: Spreading and Morphology Are Altered In Faksupporting

confidence: 54%

“…Here, we addressed this question using a mutant mouse deleted of FAK exon 15, which encodes 19 amino acids, including Tyr-397 (21). Our results show that the requirement for FAK autophosphorylation varies during development and demonstrate that the physiological functions of FAK in vivo are achieved through both autophosphorylation-independent and autophosphorylation-dependent mechanisms.…”

Section: Focal Adhesion Kinase (Fak)mentioning

confidence: 97%

See 1 more Smart Citation

Autophosphorylation-independent and -dependent Functions of Focal Adhesion Kinase during Development

Corsi

Houbron

Billuart

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) regulates numerous cellular functions and is critical for processes ranging from embryo development to cancer progression. Although autophosphorylation on Tyr-397 appears required for FAK functions in vitro, its role in vivo has not been established. We addressed this question using a mutant mouse (fak⌬) deleted of exon 15, which encodes Tyr-397. The resulting mutant protein FAK⌬ is an active kinase expressed at normal levels. Our results demonstrate that the requirement for FAK autophosphorylation varies during development. FAK ⌬/⌬ embryos developed normally up to embryonic day (E) 12.5, contrasting with the lethality at E8.5 of FAK-null embryos. Thus, autophosphorylation on Tyr-397 is not required for FAK to achieve its functions until late mid-gestation. However, FAK ⌬/⌬ embryos displayed hemorrhages, edema, delayed artery formation, vascular remodeling defects, multiple organ abnormalities, and overall developmental retardation at E13.5-14.5, and died thereafter demonstrating that FAK autophosphorylation is also necessary for normal development. Fibroblasts derived from mutant embryos had a normal stellate morphology and expression of focal adhesion proteins, Src family members, p53, and Pyk2. In contrast, in FAK ⌬/⌬ fibroblasts and endothelial cells, spreading and lamellipodia formation were altered with an increased size and number of focal adhesions, enriched in FAK⌬. FAK mutation also decreased fibroblast proliferation. These results show that the physiological functions of FAK in vivo are achieved through both autophosphorylation-independent and autophosphorylation-dependent mechanisms.Focal adhesion kinase (FAK) 2 is a nonreceptor tyrosine kinase critical for processes ranging from embryo development (1) to cancer invasiveness and metastasis (2). FAK activation following integrin engagement or stimulation of a variety of transmembrane receptors triggers its phosphorylation on tyrosine and the formation of multimolecular signaling complexes (3). FAK is enriched in focal adhesions, controlling their turnover and consequently adhesion-related processes such as spreading, migration, survival, and proliferation (1).The important physiological role of FAK is demonstrated by the lethality of its null mutation at embryonic day (E) 8.5 (4, 5). Further studies using conditional deletion showed that FAK regulates the development of the nervous system (6 -9), morphogenesis of the vascular network (5, 10, 11), and cardiac development (12-15). These reports clearly established that FAK is necessary for essential processes in vivo.In vitro studies have shown that, following its recruitment to focal adhesions, FAK autophosphorylation on Tyr-397 creates a high affinity binding site for multiple signaling proteins, including the Src family kinases (SFKs) (3). Following their binding to phospho-Tyr-397 and activation, SFKs phosphorylate other FAK residues inducing its complete activation, its interaction with other signaling proteins, and the stimulation of downstream signaling cascades (16). ...

show abstract

Section: Spreading and Morphology Are Altered In Faksupporting

confidence: 54%

Section: Focal Adhesion Kinase (Fak)mentioning

confidence: 97%

Autophosphorylation-independent and -dependent Functions of Focal Adhesion Kinase during Development

Corsi

Houbron

Billuart

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…These results reinforce the evolutionary conservation of this unique and important Pyk2-FAK survival pathway not shared by other FERM-containing proteins such as talin. Additionally, this survival pathway is independent of integrin regulation (33), as it requires FERM domain function that through evolution has maintained a high level of conservation (34).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, alternative FAK transcripts (containing exon 18a) with a premature stop codon have been detected in human brain corresponding to a putative FAK protein encompassing the FAK FERM domain (34). However, cellular and environmental context may dictate whether FAK or Pyk2 FERM domains function in a positive or negative fashion.…”

Section: In Both Fakmentioning

confidence: 99%

Pyk2 Inhibition of p53 as an Adaptive and Intrinsic Mechanism Facilitating Cell Proliferation and Survival

Lim¹,

Miller²,

Nam³

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Therefore, PYK2 expression has been shown to compensate for some functions, although not all, of FAK in cells derived from FAK knockout mice (41). In addition, it has been reported that FAK is subjected to alternative splicing of several coding or noncoding exons that are likely to have important biological functions (39). These data could explain, due to some compensatory mechanism, why the effect of FAK depletion on viral protein expression is not stronger.…”

Section: Discussionmentioning

confidence: 75%

Focal Adhesion Kinase Is Involved in Rabies Virus Infection through Its Interaction with Viral Phosphoprotein P

Fouquet

Nikolić

Larrous

et al. 2015

J Virol

View full text Add to dashboard Cite

The rabies virus (RABV) phosphoprotein P is a multifunctional protein: it plays an essential role in viral transcription and replication, and in addition, RABV P has been identified as an interferon antagonist. Here, a yeast two-hybrid screen revealed that RABV P interacts with the focal adhesion kinase (FAK). The binding involved the 106-to-131 domain, corresponding to the dimerization domain of P and the C-terminal domain of FAK containing the proline-rich domains PRR2 and PRR3. The P-FAK interaction was confirmed in infected cells by coimmunoprecipitation and colocalization of FAK with P in Negri bodies. By alanine scanning, we identified a single mutation in the P protein that abolishes this interaction. The mutant virus containing a substitution of Ala for Arg in position 109 in P (P.R109A), which did not interact with FAK, is affected at a posttranscriptional step involving protein synthesis and viral RNA replication. Furthermore, FAK depletion inhibited viral protein expression in infected cells. This provides the first evidence of an interaction of RABV with FAK that positively regulates infection. IMPORTANCERabies virus exhibits a small genome that encodes a limited number of viral proteins. To maintain efficient virus replication, some of them are multifunctional, such as the phosphoprotein P. We and others have shown that P establishes complex networks of interactions with host cell components. These interactions have revealed much about the role of P and about host-pathogen interactions in infected cells. Here, we identified another cellular partner of P, the focal adhesion kinase (FAK). Our data shed light on the implication of FAK in RABV infection and provide evidence that P-FAK interaction has a proviral function.

show abstract

Organization and post-transcriptional processing of focal adhesion kinase gene

Cited by 72 publications

References 88 publications

Autophosphorylation-independent and -dependent Functions of Focal Adhesion Kinase during Development

Autophosphorylation-independent and -dependent Functions of Focal Adhesion Kinase during Development

Pyk2 Inhibition of p53 as an Adaptive and Intrinsic Mechanism Facilitating Cell Proliferation and Survival

Focal Adhesion Kinase Is Involved in Rabies Virus Infection through Its Interaction with Viral Phosphoprotein P

Contact Info

Product

Resources

About