The diverse roles and multiple forms of focal adhesion kinase in brain

Armendáriz, Beatriz G.; Masdeu, M.; Soriano, Eduardo; Ureña, Jesús; Burgaya, Ferràn

doi:10.1111/ejn.12737

Cited by 27 publications

(12 citation statements)

References 190 publications

(278 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The adult brain exhibits high levels of tyrosine kinase activity, and the neuronal synapses are particularly enriched in both tyrosine kinases and tyrosine-phosphorylated proteins. The process of tyrosine phosphorylation is involved in regulation of synaptic activity such as depolarization, long-term potentiation (LTP), long-term depression (LTD), and ischemia [7]. Tyrosine kinase-and tyrosine phosphatase-mediated changes in phosphorylation of proteins that reside in the neuronal synapse mediate both short-term and long-lasting changes in synaptic and neuronal functions [8,9].…”

Section: The Focal Adhesion Kinase Family: It Takes Two To Tangomentioning

confidence: 99%

FAK family kinases in brain health and disease

2018

J. Mol. Clin. Med.

View full text Add to dashboard Cite

Brain disorders are now identified as one of the largest and costliest health risks throughout human life. While most brain disorders are not life threatening per se, their chronic and incurable nature renders the overall burden from these disorders much greater than would be suggested by mortality figures alone. Several neurodevelopmental conditions, including autism and dyslexia, are being diagnosed at increasing rates throughout the last few decades. Adolescence is now well recognized as a vulnerable brain developmental phase, in which mental disorders such as schizophrenia, depression, and bipolar disorder first appear. Additionally, the constant increase in life expectancy has led to a significant rise in the risk of several neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). A primary research goal of neuroscience is to decipher the molecular mechanisms that play direct roles in the pathophysiology of brain disorders, including those of the young and old alike. Research into these mechanisms will have the most significant impact on brain diseases and mental health. The focal adhesion kinase (FAK) and its homologous FAK-related proline-rich tyrosine kinase 2 (Pyk2) define a distinct family of non-receptor tyrosine kinases that are predominantly expressed in the developing as well as in the adult brain. Despite their high similarity, they are believed to fulfill distinct roles within the brain, which are partially determined by their different expression patterns, localization, and interacting proteins. Here, we provide a comprehensive and up-to-date overview of all known neuronal interactors and signaling pathways in which Pyk2 and FAK are involved. Using bioinformatics analysis and statistical tools, we validate, for the first time, the long-term hypothesis by which FAK is involved in axonal guidance and neurodevelopmental signaling, while Pyk2 has a more prominent role in functions of the adult brain, such as memory and learning. We also characterize two new and previously unidentified roles of Pyk2 in neuropathic pain signaling and neuroinflammation. Correlation of the most significant pathways for each kinase with human brain disorders revealed the involvement of Pyk2 in neurodegenerative diseases such as PD, AD, Huntington's disease (HD), and schizophrenia, while FAK was found to be mostly related to neurodevelopmental disorders in which axonal guidance plays a major role, and to a lesser extent to amyotrophic lateral sclerosis (ALS), schizophrenia, mood disorders, and AD. The involvement of FAK in these non-developmental pathways may suggest its possible role in compensating for Pyk2 in specific processes and/or brain disorders. Understanding the molecular mechanisms underlying regulation of FAK family proteins in brain and behavior may lead to novel therapeutic approaches for preventing or treating the underlying causes of neurodevelopmental abnormalities, psychiatric disorders, and neurodegenerative diseases.

show abstract

Section: The Focal Adhesion Kinase Family: It Takes Two To Tangomentioning

confidence: 99%

FAK family kinases in brain health and disease

2018

J. Mol. Clin. Med.

View full text Add to dashboard Cite

show abstract

“…This suggests a putative more specific role of this FAK isoform in the interaction of the cell with its support. Interestingly, the box 28 coded by exon 13, maintained in the FAK 28 mRNA variant, exhibits an inversed consensus sequence for calmodulin, which could favor the binding of FAK to cell adhesion molecules . These data suggest an eventual role of this splice variant in the regulation of cells with their direct environment by the modulation of the functions of cell adhesion molecules.…”

Section: Discussionmentioning

confidence: 92%

FAK alternative splice mRNA variants expression pattern in colorectal cancer

Devaud

Tilkin–Mariamé

Vignolle‐Vidoni

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

The Focal adhesion kinase (FAK) is a ubiquitous cytoplasmic tyrosine‐kinase promoting tumor progression and metastasis processes by acting in cancer cells and their tumor microenvironment partners. FAK overexpression in primary colon tumors and their metastasis is associated to poor colorectal cancer (CRC) patients’ outcome. Eight FAK mRNA alternative splice variants have been described and contribute to additional level of FAK activity regulation, some of them corresponding to overactivated FAK isoforms. To date, FAK mRNA alternative splice variants expression and implication in CRC processes remain unknown. Here, using different human CRC cells lines displaying differential invasive capacities in an in vivo murine model recapitulating the different steps of CRC development from primary tumors to liver and lung metastasis, we identified three out of the eight mRNA variants (namely FAK0, FAK28 and FAK6) differentially expressed along the CRC process and the tumor sites. Our results highlight an association between FAK0 and FAK6 expressions and the metastatic potential of the most aggressive cell lines HT29 and HCT116, suggesting that FAK0 and FAK6 could represent aggressiveness markers in CRC. Our findings also suggest a more specific role for FAK28 in the interactions between the tumors cells and their microenvironment. In conclusion, targeting FAK0, the common form of FAK, might not be a good strategy based on the numerous roles of this kinase in physiological processes. In contrast, FAK6 or FAK28 splice variants, or their corresponding protein isoforms, may putatively represent future therapeutic target candidates in the development of CRC primary tumors and metastasis.

show abstract

“…Decreases in the areas of focal adhesion complexes (FACs) and FAK activation (pY397-FAK) were observed in C17.2 cells after exposure to gold NPs [29]. FACs form a direct link between the intracellular actin network and the extracellular matrix Studies have indicated that FACs and FAK play vital roles in cytoskeletal stabilization and cellular migration processes [36]. Furthermore, high intracellular levels of iron oxide NPs were observed to disrupt cytoskeletal components, e.g., MTs and MFs, as well as affect the expression of FAKs and the level of activated FAK [37].…”

Section: Cellular Physiological Activity Changesmentioning

confidence: 99%

Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

Kang¹,

Liu²,

Song³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Inorganic nanomaterials have been widely applied in biomedicine. However, several studies have noted that inorganic nanoparticles can enter the brain and induce cytoskeletal remodeling, as well as electrophysiological alterations, which are related to neurodevelopmental disorders and neurodegenerative diseases. The toxic effects of inorganic nanomaterials on the cytoskeleton and electrophysiology are summarized in this review. The relationships between inorganic NPs-induced cytoskeletal and electrophysiological alterations in the central nervous system remain obscure. We propose several potential relationships, including those involving N-methyl-D-aspartate receptor function, ion channels, transient receptor potential channels, and the Rho pathway.

show abstract

The diverse roles and multiple forms of focal adhesion kinase in brain

Cited by 27 publications

References 190 publications

FAK family kinases in brain health and disease

FAK family kinases in brain health and disease

FAK alternative splice mRNA variants expression pattern in colorectal cancer

Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

Contact Info

Product

Resources

About