Fak

Summary

Gene Symbol: Fak
Description: Focal adhesion kinase
Alias: CG10023, CT28129, DFAK, DFak, DFak56, Dfak, Dfak56, DmFAK, Dmel\CG10023, FAK, FAK65D, Fak56, Fak56D, dFak, fak, fak56, pFAK, ptk2, focal adhesion kinase, CG10023-PA, CG10023-PB, CG10023-PC, CG10023-PD, CG10023-PF, CG10023-PG, Fak-PA, Fak-PB, Fak-PC, Fak-PD, Fak-PF, Fak-PG, focal adhesion kinase homolog, protein tyrosine kinase 2
Species: fruit fly

Top Publications

  1. Tanentzapf G, Martin Bermudo M, Hicks M, Brown N. Multiple factors contribute to integrin-talin interactions in vivo. J Cell Sci. 2006;119:1632-44 pubmed
    ..Mutagenesis of the integrin cytoplasmic domain, within the chimera, showed the dominant-negative inhibition was not due to talin sequestration alone and that additional interactions are required. ..
  2. Lo S. Focal adhesions: what's new inside. Dev Biol. 2006;294:280-91 pubmed
    ..Recent studies using genetic approaches in invertebrate and vertebrate systems have begun to reveal the structure and function of these complexes in vivo. ..
  3. Nguyen H, Voza F, Ezzeddine N, Frasch M. Drosophila mind bomb2 is required for maintaining muscle integrity and survival. J Cell Biol. 2007;179:219-27 pubmed
    ..Our data suggest strongly that mib2 is involved in a novel Notch- and integrin-independent pathway that maintains the integrity of fully differentiated muscles and prevents their apoptotic degeneration. ..
  4. Torgler C, Narasimha M, Knox A, Zervas C, Vernon M, Brown N. Tensin stabilizes integrin adhesive contacts in Drosophila. Dev Cell. 2004;6:357-69 pubmed
  5. Fox G, Rebay I, Hynes R. Expression of DFak56, a Drosophila homolog of vertebrate focal adhesion kinase, supports a role in cell migration in vivo. Proc Natl Acad Sci U S A. 1999;96:14978-83 pubmed
    b>Focal adhesion kinase (FAK) is a highly conserved, cytoplasmic tyrosine kinase that has been implicated in promoting cell migration and transmission of antiapoptotic signals in vertebrate cells...
  6. Tanentzapf G, Brown N. An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton. Nat Cell Biol. 2006;8:601-6 pubmed
    ..However, it reduced the ability of talin to strengthen integrin adhesion to the ECM, indicating that the function of the talin-head-NPxY interaction is solely to regulate integrin adhesion. ..
  7. Ellis S, Goult B, Fairchild M, Harris N, Long J, Lobo P, et al. Talin autoinhibition is required for morphogenesis. Curr Biol. 2013;23:1825-33 pubmed publisher
    ..Based on our data, we propose that talin autoinhibition provides a switch for modulating adhesion turnover and adhesion stability that is essential for morphogenesis. ..
  8. Fernández Miñán A, Martin Bermudo M, González Reyes A. Integrin signaling regulates spindle orientation in Drosophila to preserve the follicular-epithelium monolayer. Curr Biol. 2007;17:683-8 pubmed
    ..The above data show that integrins are necessary for preserving the simple organization of a specialized epithelium and link integrin-mediated signaling to the correct orientation of the mitotic spindle in this epithelial cell type. ..
  9. Ueda A, Grabbe C, Lee J, Lee J, Palmer R, Wu C. Mutation of Drosophila focal adhesion kinase induces bang-sensitive behavior and disrupts glial function, axonal conduction and synaptic transmission. Eur J Neurosci. 2008;27:2860-70 pubmed publisher
    The role of the conserved focal adhesion kinase (FAK) family of protein tyrosine kinases in the development and physiological functions of the CNS has long been an area of interest among neuroscientists...

More Information

Publications59

  1. Tsai P, Kao H, Grabbe C, Lee Y, Ghose A, Lai T, et al. Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth. Neural Dev. 2008;3:26 pubmed publisher
    b>Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade...
  2. Grabbe C, Zervas C, Hunter T, Brown N, Palmer R. Focal adhesion kinase is not required for integrin function or viability in Drosophila. Development. 2004;131:5795-805 pubmed
    The mammalian focal adhesion kinase (FAK) family of non-receptor protein-tyrosine kinases has been implicated in controlling a multitude of cellular responses to the engagement of cell-surface integrins and G-protein-coupled receptors...
  3. Fujimoto J, Sawamoto K, Okabe M, Takagi Y, Tezuka T, Yoshikawa S, et al. Cloning and characterization of Dfak56, a homolog of focal adhesion kinase, in Drosophila melanogaster. J Biol Chem. 1999;274:29196-201 pubmed
    The focal adhesion kinase (FAK) protein-tyrosine kinase plays important roles in cell adhesion in vertebrates...
  4. Murakami S, Umetsu D, Maeyama Y, Sato M, Yoshida S, Tabata T. Focal adhesion kinase controls morphogenesis of the Drosophila optic stalk. Development. 2007;134:1539-48 pubmed
    ..genes involved in optic stalk formation, we identified Fak56D encoding a Drosophila homolog of mammalian focal adhesion kinase (FAK)...
  5. Palmer R, Fessler L, Edeen P, Madigan S, McKeown M, Hunter T. DFak56 is a novel Drosophila melanogaster focal adhesion kinase. J Biol Chem. 1999;274:35621-9 pubmed
    The mammalian focal adhesion kinase (FAK) family of nonreceptor protein-tyrosine kinases have been implicated in controlling a multitude of cellular responses to the engagement of cell surface integrins and G protein-coupled receptors...
  6. Geisbrecht E, Montell D. Myosin VI is required for E-cadherin-mediated border cell migration. Nat Cell Biol. 2002;4:616-20 pubmed
    ..Multiple biochemical mechanisms may exist, therefore, for cadherins to associate with diverse unconventional myosins that are required for normal stereocilium formation or maintenance. ..
  7. Tikhmyanova N, Tulin A, Roegiers F, Golemis E. Dcas supports cell polarization and cell-cell adhesion complexes in development. PLoS ONE. 2010;5:e12369 pubmed publisher
    ..of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A...
  8. Pérez Pepe M, Slomiansky V, Loschi M, Luchelli L, Neme M, Thomas M, et al. BUHO: a MATLAB script for the study of stress granules and processing bodies by high-throughput image analysis. PLoS ONE. 2012;7:e51495 pubmed publisher
    ..We found that FAK56D, GCN2 and PP1 govern SG formation...
  9. Bahri S, Choy J, Manser E, Lim L, Yang X. The Drosophila homologue of Arf-GAP GIT1, dGIT, is required for proper muscle morphogenesis and guidance during embryogenesis. Dev Biol. 2009;325:15-23 pubmed publisher
    ..We propose that dGIT and dPak are part of a complex that promotes proper muscle morphogenesis and myotube targeting during embryogenesis. ..
  10. Sterne G, Kim J, Ye B. Dysregulated Dscam levels act through Abelson tyrosine kinase to enlarge presynaptic arbors. elife. 2015;4: pubmed publisher
    ..This study offers Abl as a potential therapeutic target for treating brain disorders associated with dysregulated Dscam expression. ..
  11. Cho J, Chak K, Andreone B, Wooley J, Kolodkin A. The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance. Genes Dev. 2012;26:2222-35 pubmed publisher
    ..Perlecan augments the reduction in phospho-focal adhesion kinase (phospho-FAK) levels that result from treating insect cells in vitro with Sema-1a, and genetic ..
  12. Momota R, Narasaki M, Komiyama T, Naito I, Ninomiya Y, Ohtsuka A. Drosophila type XV/XVIII collagen mutants manifest integrin mediated mitochondrial dysfunction, which is improved by cyclosporin A and losartan. Int J Biochem Cell Biol. 2013;45:1003-11 pubmed publisher
    ..In addition, mutants' IFMs exhibited diminished ?PS integrin clustering and abolished focal adhesion kinase (FAK) phosphorylation...
  13. Lee J, Chen J, Shaw J, Chang K. Maintenance of Stem Cell Niche Integrity by a Novel Activator of Integrin Signaling. PLoS Genet. 2016;12:e1006043 pubmed publisher
  14. Silver D, Montell D. Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila. Cell. 2001;107:831-41 pubmed
    ..Ectopic expression of either UPD or JAK is sufficient to induce extra epithelial cells to migrate. Thus, a localized signal activates the JAK/STAT pathway in neighboring epithelial cells, causing them to become invasive. ..
  15. Weitkunat M, Kaya Copur A, Grill S, Schnorrer F. Tension and force-resistant attachment are essential for myofibrillogenesis in Drosophila flight muscle. Curr Biol. 2014;24:705-16 pubmed publisher
    ..As myofibril and sarcomeric architecture as well as their molecular components are evolutionarily conserved, we propose a similar tension-based mechanism to regulate myofibrillogenesis in vertebrates. ..
  16. Jin S, Hu G, Qian Y, Zhang L, Zhang J, Qiu G, et al. Identification of one intron loss and phylogenetic evolution of Dfak gene in the Drosophila melanogaster species group. Genetica. 2005;125:223-30 pubmed
    ..The current study provides another example of intron loss within a single-copy Dfak gene in Drosophila. By using polymerase chain reaction (PCR), we amplified about 1...
  17. Goulas S, Conder R, Knoblich J. The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells. Cell Stem Cell. 2012;11:529-40 pubmed publisher
    ..Our data indicate that mechanisms for intrinsically asymmetric cell division can be adapted to allow for the flexibility in lineage decisions that is required in adult stem cells. ..
  18. Pandur P, Maurus D, Kuhl M. Increasingly complex: new players enter the Wnt signaling network. Bioessays. 2002;24:881-4 pubmed
  19. Ellis S, Lostchuck E, Goult B, Bouaouina M, Fairchild M, López Ceballos P, et al. The talin head domain reinforces integrin-mediated adhesion by promoting adhesion complex stability and clustering. PLoS Genet. 2014;10:e1004756 pubmed publisher
    ..We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development. ..
  20. Dibya D, Sander S, Smith E. Identifying cytoplasmic proteins that affect receptor clustering using fluorescence resonance energy transfer and RNA interference. Anal Bioanal Chem. 2009;395:2303-11 pubmed publisher
    ..targeted in this study include: dreadlock, integrin-linked kinase, paxillin, steamer duck, vinculin, rhea, focal adhesion kinase, and actin 42A...
  21. Chen D, Li M, Wu S, Lin Y, Tsai S, Lai P, et al. The Bro1-domain-containing protein Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration. J Cell Sci. 2012;125:4841-52 pubmed publisher
    ..Depletion of HDPTP resulted in actin reorganization and increased cell motility. Together, our findings suggest an evolutionarily conserved function of HDPTP-Rab4 in the regulation of endocytic trafficking, cell adhesion and migration. ..
  22. Cadigan K. Wnt signaling--20 years and counting. Trends Genet. 2002;18:340-2 pubmed
  23. Bai J, Uehara Y, Montell D. Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell. 2000;103:1047-58 pubmed
    ..Mutant cells exhibited abnormal accumulation of E-cadherin, beta-catenin, and focal adhesion kinase. TAI protein colocalized with the ecdysone receptor in vivo and augmented transcriptional activation by ..
  24. Montell D. Command and control: regulatory pathways controlling invasive behavior of the border cells. Mech Dev. 2001;105:19-25 pubmed
    ..that is required for elevated expression of a number of downstream targets, including DE-cadherin and focal adhesion kinase (FAK)...
  25. Moreira C, Jacinto A, Prag S. Drosophila integrin adhesion complexes are essential for hemocyte migration in vivo. Biol Open. 2013;2:795-801 pubmed publisher
    ..Our data point to mechanisms of cell migration similar to those described in three-dimensional in vitro systems and other in vivo model organisms. ..
  26. Xu D, Shen W, Guo R, Xue Y, Peng W, Sima J, et al. Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci. 2013;16:1238-47 pubmed publisher
    ..Expression of one such gene, that encoding protein tyrosine kinase 2 (ptk2, also known as focal adhesion kinase or FAK), is reduced in the neuromuscular junctions of Top3β..
  27. Tsai P, Wang M, Kao H, Cheng Y, Walker J, Chen R, et al. Neurofibromin mediates FAK signaling in confining synapse growth at Drosophila neuromuscular junctions. J Neurosci. 2012;32:16971-81 pubmed publisher
    ..NF1 functions downstream of the Drosophila focal adhesion kinase (FAK) Fak56 and physically interacts with Fak56...
  28. Zhan L, Tian J, Liu C, Ke F, Yang Y, Li C, et al. An intron loss of Dfak gene in species of the Drosophila melanogaster subgroup and phylogenetic analysis. J Hered. 2008;99:417-20 pubmed publisher
    Drosophila focal adhesion kinase (Dfak) gene is a single-copy nuclear gene. Previous study revealed that Drosophila melanogaster and Drosophila simulans had lost an intron precisely within the tyrosine kinase (TyK) domain of this gene...
  29. Geisbrecht E, Montell D. A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Cell. 2004;118:111-25 pubmed
    ..These results indicate an apoptosis-independent role for DIAP1-mediated Dronc inhibition in Rac-mediated cell motility. ..
  30. Chun Jen Lin C, Summerville J, Howlett E, Stern M. The metabotropic glutamate receptor activates the lipid kinase PI3K in Drosophila motor neurons through the calcium/calmodulin-dependent protein kinase II and the nonreceptor tyrosine protein kinase DFak. Genetics. 2011;188:601-13 pubmed publisher
    ..Here we identify CaMKII and the nonreceptor tyrosine kinase DFak as critical intermediates in the DmGluRA-dependent activation of PI3K at Drosophila motor nerve terminals...
  31. Yu J, Wu H, Wen Y, Liu Y, Zhou T, Ni B, et al. Identification of seven genes essential for male fertility through a genome-wide association study of non-obstructive azoospermia and RNA interference-mediated large-scale functional screening in Drosophila. Hum Mol Genet. 2015;24:1493-503 pubmed publisher
    ..Our study thus demonstrates that SNPs without genome-wide significance in GWAS may also provide clues to disease-related genes and therefore warrant functional analysis. ..
  32. Macagno J, Díaz Vera J, Yu Y, MacPherson I, Sandilands E, Palmer R, et al. FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells. PLoS Genet. 2014;10:e1004262 pubmed publisher
    Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway...
  33. You J, Zhang Y, Li Z, Lou Z, Jin L, Lin X. Drosophila perlecan regulates intestinal stem cell activity via cell-matrix attachment. Stem Cell Reports. 2014;2:761-9 pubmed publisher
    ..We propose that Pcan secreted by ISCs confers niche properties to the adjacent ECM that is required for ISC maintenance of stem cell identity, activity, and anchorage to the niche. ..
  34. Pronovost S, Beckerle M, Kadrmas J. Elevated expression of the integrin-associated protein PINCH suppresses the defects of Drosophila melanogaster muscle hypercontraction mutants. PLoS Genet. 2013;9:e1003406 pubmed publisher
    ..Moreover, in myopathies that exhibit hypercontraction, strategic PINCH expression may have therapeutic potential in preserving muscle structure and function. ..
  35. McDonald J, Khodyakova A, Aranjuez G, Dudley C, Montell D. PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells. Curr Biol. 2008;18:1659-67 pubmed publisher
    ..Thus, this work reveals new insights into two distinct, but essential, steps of epithelial cell migration. ..
  36. Williams M, Wiklund M, Wikman S, Hultmark D. Rac1 signalling in the Drosophila larval cellular immune response. J Cell Sci. 2006;119:2015-24 pubmed
    ..Furthermore, Rac1 and Bsk are involved in regulating the formation of actin- and focal adhesion kinase (FAK)-rich placodes in hemocytes...
  37. Liu Z, Odell N, Geisbrecht E. Drosophila importin-7 functions upstream of the Elmo signaling module to mediate the formation and stability of muscle attachments. J Cell Sci. 2013;126:5210-23 pubmed publisher
    ..Our results show that integrins function as upstream signals to mediate Dim7-Elmo enrichment to the MASs. ..
  38. Delon I, Brown N. The integrin adhesion complex changes its composition and function during morphogenesis of an epithelium. J Cell Sci. 2009;122:4363-74 pubmed publisher
    ..Molecular variation of the integrin complex is thus a key component of developmentally programmed morphogenesis. ..
  39. Lee Y, Reinhardt J. Widespread polymorphism in the positions of stop codons in Drosophila melanogaster. Genome Biol Evol. 2012;4:533-49 pubmed publisher
    ..melanogaster and Drosophila simulans, and high-frequency alleles that cause extreme changes in gene length. SCPs likely have an important role in the evolution of these genes. ..
  40. Alves Silva J, Hahn I, Huber O, Mende M, Reissaus A, Prokop A. Prominent actin fiber arrays in Drosophila tendon cells represent architectural elements different from stress fibers. Mol Biol Cell. 2008;19:4287-97 pubmed publisher
    ..Features reported here and elsewhere for tendon cells are reminiscent of the structural and molecular features of support cells in the inner ear of vertebrates, and they might have potential translational value. ..
  41. Ribeiro S, D Ambrosio M, Vale R. Induction of focal adhesions and motility in Drosophila S2 cells. Mol Biol Cell. 2014;25:3861-9 pubmed publisher
    ..fluctuations of focal adhesions were decreased by RNA interference (RNAi) depletion of myosin II and focal adhesion kinase, suggesting that this behavior requires force and focal adhesion maturation...
  42. Dani N, Zhu H, Broadie K. Two protein N-acetylgalactosaminyl transferases regulate synaptic plasticity by activity-dependent regulation of integrin signaling. J Neurosci. 2014;34:13047-65 pubmed publisher
    ..Critically, acute blockade of integrin signaling acts synergistically with pgant mutants to eliminate all activity-dependent synaptic plasticity. ..
  43. Chen G, Lee J, Tang H, Debnath J, Thomas S, Settleman J. Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation. Autophagy. 2008;4:37-45 pubmed
    ..Together, these findings reveal a novel evolutionarily conserved role for paxillin in autophagy. ..
  44. Meltzer S, Yadav S, Lee J, Soba P, Younger S, Jin P, et al. Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons. Neuron. 2016;89:741-55 pubmed publisher
    ..These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly. ..
  45. Cohen E, Mariol M, Wallace R, Weyers J, Kamberov Y, Pradel J, et al. DWnt4 regulates cell movement and focal adhesion kinase during Drosophila ovarian morphogenesis. Dev Cell. 2002;2:437-48 pubmed
    ..One of these factors, focal adhesion kinase (FAK), regulates the cycle of focal adhesion formation and disassembly that is required for cell movement ..
  46. Sawala A, Scarcia M, Sutcliffe C, Wilcockson S, Ashe H. Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling. Cell Rep. 2015;12:1584-93 pubmed publisher
    ..The BMP-pathway-enhancing function of integrins is independent of focal adhesion kinase, but it requires conserved NPXY motifs in the β-integrin cytoplasmic tail...
  47. Sander M, Squarr A, Risse B, Jiang X, Bogdan S. Drosophila pupal macrophages--a versatile tool for combined ex vivo and in vivo imaging of actin dynamics at high resolution. Eur J Cell Biol. 2013;92:349-54 pubmed publisher
  48. Schardt L, Ander J, Lohmann I, Papagiannouli F. Stage-specific control of niche positioning and integrity in the Drosophila testis. Mech Dev. 2015;138 Pt 3:336-48 pubmed publisher
  49. Tsai P, Wang M, Kao H, Cheng Y, Lin Y, Chen R, et al. Activity-dependent retrograde laminin A signaling regulates synapse growth at Drosophila neuromuscular junctions. Proc Natl Acad Sci U S A. 2012;109:17699-704 pubmed publisher
    ..The presynaptic integrin pathway consists of the integrin subunit ?? and focal adhesion kinase 56 (Fak56), both of which are required to suppress crawling activity-dependent NMJ growth...
  50. Liu Z, Geisbrecht E. Moleskin is essential for the formation of the myotendinous junction in Drosophila. Dev Biol. 2011;359:176-89 pubmed publisher
    ..However, msk mutants fail to localize phosphorylated focal adhesion kinase (pFAK) to the sites of muscle-tendon cell junctions...