Biology:PTK2

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene.[1] PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around).[2] It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.[3]

Function

The PTK2 gene encodes a cytosolic protein tyrosine kinase that is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant sequence similarity to kinases from other subfamilies. It also includes a large FERM domain.[4][5]

With the exception of certain types of blood cells, most cells express FAK. FAK tyrosine kinase activity can be activated, which plays a key important early step in cell migration. FAK activity elicits intracellular signal transduction pathways that promote the turn-over of cell contacts with the extracellular matrix, promoting cell migration. FAK is required during development, with loss of FAK resulting in lethality. It seems to be a paradox that FAK is not absolutely required for cell migration, and may play other roles in the cell, including the regulation of the tumor suppressor p53. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined.[6]

FAK is a protein of 125 kD recruited as a participant in focal adhesion dynamics between cells, and has a role in motility and cell survival. FAK is a highly conserved, non-receptor tyrosine kinase originally identified as a substrate for the oncogene protein tyrosine kinase v-src.[7] This cytosolic kinase has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. FAK is typically located at structures known as focal adhesions, which are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton. Additional components of focal adhesions include actin, filamin, vinculin, talin, paxillin, tensin[8] and RSU-1.

Regulation

FAK is phosphorylated in response to integrin engagement, growth factor stimulation, and the action of mitogenic neuropeptides.[9][10] Integrin receptors are heterodimeric transmembrane glycoproteins that cluster upon ECM engagement, leading to FAK phosphorylation and recruitment to focal adhesions.[11][12] FAK activity can also be attenuated by expression of its endogenous inhibitor known as FAK-related nonkinase (FRNK). This is a truncated protein consisting of only the carboxyl-terminal noncatalytic domain of FAK.[13]

Role in apoptosis

During early apoptotic signaling in human endothelial cells, FAK is cleaved by caspase 3 at Asp-772, generating two FAK fragments of approximately 90 and 130 kDa in length.[14] The smaller FAK fragment is termed "killer FAT" and becomes the domain associated with death signaling.[14] Throughout apoptosis, FAK is an important contributor to cell rounding, loss of focal contacts and apoptotic membrane formations such as blebbing,[15] which involves contracting the cortical actin ring and is followed by chromatin condensation and nuclear fragmentation.[16] Overexpression of FAK leads to inhibition of apoptosis and an increase in the prevalence of metastatic tumors.[15]

Structure

Focal adhesion kinase has four defined regions, or tertiary structure domains. Two of these domains, the N-terminal FERM domain and the Kinase domain form an auto-inhibitory interaction. This interaction—thought to be the result of hydrophobic interactions between the two domains[17]—prevents the activation of the Kinase domain, thereby preventing the signalling function of FAK. Release of this auto-inhibitory interaction has been shown to occur within focal adhesions—but not in the cytoplasm—and therefore is thought to require interaction with focal adhesion proteins, potentially as a result of mechanical forces transmitted through the focal adhesion.

C-terminus

A carboxy-terminal region of one hundred and fifty-nine amino acids, the focal adhesion targeting domain (FAT), has been shown to be responsible for targeting FAK to focal adhesions.[18] This domain is composed of four alpha helices arranged in a bundle. The N-terminal helix contains a phosphorylatable tyrosine (Y925) implicated in signal transduction. Two hydrophobic patches between helices—one formed by the first and fourth helix, the other formed by the second and third helix—have been shown to bind short helical domains of Paxillin.[19]

N-terminus

The function of the amino-terminal domain is less clear, but it has been shown to interact with the beta-1 integrin subunit in vitro and is thought to be involved in the transduction of signals from ECM-integrin clusters.[20] However, a study has called into question the importance of this interaction and suggested that interaction with the cytoplasmic region of the beta-3 integrin subunit is important.[21]

The amino-terminal domains of FAK share a significant sequence similarity with the band 4.1 domain first identified in erythrocytes. This 4.1 band domain binds to the cytoplasmic region of transmembrane proteins including glycophorin C, actin and spectrin.[22] This suggests that the amino-terminal region of FAK may have a role in anchoring the cytoskeleton, the exact nature of this role has not been clarified as yet.

Catalytic/regulatory domain

Between the amino and the carboxy regions lies the catalytic domain. Phosphorylation of the activation loop within this kinase domain is important for the kinase activity of FAK.[23]

Clinical significance

FAK mRNA levels are elevated in ~37% of serous ovarian tumors and ~26% of invasive breast cancers, and in several other malignancies.[24]

As a drug target

FAK inhibitors

Because of the involvement of FAK in many cancers, drugs that inhibit FAK are being sought and evaluated,[25] e.g. in 2012: PF-573,228 (PF-228), PF-562,271 (PF-271), NVP-226, Y15 (1,2,4,5-benzenetetraamine tetrahydrochloride), and PND-1186,[25]

By 2013 GSK2256098 and PF-573,228 had completed at least one phase 1 trial.[25]

Additional FAK inhibitors in clinical trials in 2014 were:[24] VS-6062 (PF 562,271), VS-6063 (PF-04554878 defactinib) and VS-4718 (PND-1186) (all three are ATP-competitive kinase inhibitors). VS-6063 was in a phase II trial in patients with KRAS mutant non-small cell lung cancer (Trial ID: NCT01951690) to see how the response depends on tumor-associated INK4a/Arf and p53 mutations.[24]

In 2015, a mesothelioma trial of VS-6063 was ended early due to 'poor performance'.[26]

Interactions

PTK2 has been shown to interact with:


See also

References

  1. ↑ "Expression of an N-terminally truncated form of human focal adhesion kinase in brain". Biochemical and Biophysical Research Communications 190 (1): 140–7. January 1993. doi:10.1006/bbrc.1993.1022. PMID 8422239. 
  2. ↑ Blackshaw, S. E.; Dow, J. Kamal; Lackie, J. M. (1999). The dictionary of cell and molecular biology (3rd ed.). San Diego: Academic Press. ISBN 978-0-12-432565-4. 
  3. ↑ "FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion". The Journal of Cell Biology 185 (2): 357–70. 2009. doi:10.1083/jcb.200809110. PMID 19364917. 
  4. ↑ SCOPe: Structural Classification of Proteins — extended. Release 2.06. Lineage for Protein: Focal adhesion kinase 1
  5. ↑ Q00944
  6. ↑ "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5747. 
  7. ↑ "Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation". Nature 358 (6388): 690–2. August 1992. doi:10.1038/358690a0. PMID 1379699. Bibcode: 1992Natur.358..690G. 
  8. ↑ "Rho-stimulated contractility drives the formation of stress fibers and focal adhesions". The Journal of Cell Biology 133 (6): 1403–15. June 1996. doi:10.1083/jcb.133.6.1403. PMID 8682874. 
  9. ↑ "Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells". The Journal of Biological Chemistry 272 (24): 15442–51. June 1997. doi:10.1074/jbc.272.24.15442. PMID 9182576. 
  10. ↑ "Focal adhesion kinase (p125FAK): a point of convergence in the action of neuropeptides, integrins, and oncogenes". Cell 71 (6): 891–4. December 1992. doi:10.1016/0092-8674(92)90385-P. PMID 1458538. 
  11. ↑ "Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton". Annual Review of Cell Biology 4: 487–525. 1988. doi:10.1146/annurev.cb.04.110188.002415. PMID 3058164. https://cdr.lib.unc.edu/concern/articles/4j03d211n. 
  12. ↑ "Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly". The Journal of Cell Biology 119 (4): 893–903. November 1992. doi:10.1083/jcb.119.4.893. PMID 1385444. 
  13. ↑ "Selective expression of an endogenous inhibitor of FAK regulates proliferation and migration of vascular smooth muscle cells". Molecular and Cellular Biology 21 (5): 1565–72. March 2001. doi:10.1128/MCB.21.5.1565-1572.2001. PMID 11238893. 
  14. ↑ 14.0 14.1 "Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130cas, and Nck adaptor proteins". Molecular and Cellular Biology 17 (3): 1702–13. March 1997. doi:10.1128/mcb.17.3.1702. PMID 9032297. 
  15. ↑ 15.0 15.1 "Metastasis: a question of life or death". Nature Reviews. Cancer 6 (6): 449–58. June 2006. doi:10.1038/nrc1886. PMID 16723991. 
  16. ↑ "Cytoskeleton and apoptosis". Biochemical Pharmacology 76 (1): 11–8. July 2008. doi:10.1016/j.bcp.2008.03.016. PMID 18462707. 
  17. ↑ "Structural basis for the autoinhibition of focal adhesion kinase". Cell 129 (6): 1177–87. June 2007. doi:10.1016/j.cell.2007.05.041. PMID 17574028. 
  18. ↑ "Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions". The Journal of Cell Biology 123 (4): 993–1005. November 1993. doi:10.1083/jcb.123.4.993. PMID 8227154. 
  19. ↑ "Paxillin, a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase". Molecular Biology of the Cell 6 (6): 637–47. June 1995. doi:10.1091/mbc.6.6.637. PMID 7579684. 
  20. ↑ "Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains". The Journal of Cell Biology 130 (5): 1181–7. September 1995. doi:10.1083/jcb.130.5.1181. PMID 7657702. 
  21. ↑ "The role of conserved amino acid motifs within the integrin beta3 cytoplasmic domain in triggering focal adhesion kinase phosphorylation". The Journal of Biological Chemistry 272 (12): 7892–8. March 1997. doi:10.1074/jbc.272.12.7892. PMID 9065456. 
  22. ↑ "Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure and signal transduction". Molecular Medicine 4 (12): 751–69. December 1998. doi:10.1007/BF03401769. PMID 9990861. 
  23. ↑ "Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases". Molecular and Cellular Biology 15 (2): 954–63. February 1995. doi:10.1128/MCB.15.2.954. PMID 7529876. 
  24. ↑ 24.0 24.1 24.2 "FAK in cancer: mechanistic findings and clinical applications". Nature Reviews. Cancer 14 (9): 598–610. September 2014. doi:10.1038/nrc3792. PMID 25098269. 
  25. ↑ 25.0 25.1 25.2 "Evolving therapies and FAK inhibitors for the treatment of cancer". Anti-Cancer Agents in Medicinal Chemistry 10 (10): 722–34. December 2010. doi:10.2174/187152010794728657. PMID 21291406. 
  26. ↑ Researchers Stop Once-Promising Mesothelioma Clinical Trial. Oct 2015
  27. ↑ "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". The Journal of Biological Chemistry 271 (41): 25198–203. October 1996. doi:10.1074/jbc.271.41.25198. PMID 8810278. 
  28. ↑ 28.0 28.1 28.2 "Differential regulation of cell motility and invasion by FAK". The Journal of Cell Biology 160 (5): 753–67. March 2003. doi:10.1083/jcb.200212114. PMID 12615911. 
  29. ↑ 29.0 29.1 "An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Molecular and Cellular Biology 16 (6): 3169–78. June 1996. doi:10.1128/MCB.16.6.3169. PMID 8649427. 
  30. ↑ "Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin". The Journal of Biological Chemistry 276 (50): 47434–44. December 2001. doi:10.1074/jbc.M107494200. PMID 11577104. 
  31. ↑ "Activation of Wiskott-Aldrich syndrome protein and its association with other proteins by stromal cell-derived factor-1alpha is associated with cell migration in a T-lymphocyte line". Experimental Hematology 30 (7): 761–6. July 2002. doi:10.1016/s0301-472x(02)00823-8. PMID 12135674. 
  32. ↑ 32.0 32.1 "Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C". Blood 95 (8): 2505–13. April 2000. doi:10.1182/blood.V95.8.2505. PMID 10753828. 
  33. ↑ "Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain". Nature Cell Biology 3 (5): 439–44. May 2001. doi:10.1038/35074500. PMID 11331870. 
  34. ↑ 34.0 34.1 "Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling". The Journal of Cell Biology 157 (1): 149–60. April 2002. doi:10.1083/jcb.200109079. PMID 11927607. 
  35. ↑ 35.0 35.1 "Thrombspondin acts via integrin-associated protein to activate the platelet integrin alphaIIbbeta3". The Journal of Biological Chemistry 272 (23): 14740–6. June 1997. doi:10.1074/jbc.272.23.14740. PMID 9169439. 
  36. ↑ 36.0 36.1 36.2 "Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts". The Journal of Cell Biology 144 (5): 1019–31. March 1999. doi:10.1083/jcb.144.5.1019. PMID 10085298. 
  37. ↑ 37.0 37.1 "Focal adhesion kinase in netrin-1 signaling". Nature Neuroscience 7 (11): 1204–12. November 2004. doi:10.1038/nn1330. PMID 15494733. 
  38. ↑ 38.0 38.1 38.2 "Specific interactions of neuronal focal adhesion kinase isoforms with Src kinases and amphiphysin". Journal of Neurochemistry 84 (2): 253–65. January 2003. doi:10.1046/j.1471-4159.2003.01519.x. PMID 12558988. 
  39. ↑ "The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases". The Journal of Biological Chemistry 276 (20): 17199–205. May 2001. doi:10.1074/jbc.M011185200. PMID 11278857. 
  40. ↑ "Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting". The Journal of Neuroscience 23 (5): 1667–77. March 2003. doi:10.1523/JNEUROSCI.23-05-01667.2003. PMID 12629171. 
  41. ↑ "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". The Journal of Biological Chemistry 278 (8): 6291–300. February 2003. doi:10.1074/jbc.M212287200. PMID 12473661. 
  42. ↑ "Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly". Molecular and Cellular Biology 20 (17): 6354–63. September 2000. doi:10.1128/MCB.20.17.6354-6363.2000. PMID 10938112. 
  43. ↑ "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of Biological Chemistry 274 (34): 24425–30. August 1999. doi:10.1074/jbc.274.34.24425. PMID 10446223. 
  44. ↑ "FAK integrates growth-factor and integrin signals to promote cell migration". Nature Cell Biology 2 (5): 249–56. May 2000. doi:10.1038/35010517. PMID 10806474. http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-41292. 
  45. ↑ "The structural basis of localization and signaling by the focal adhesion targeting domain". Structure 10 (3): 319–27. March 2002. doi:10.1016/s0969-2126(02)00717-7. PMID 12005431. 
  46. ↑ 46.0 46.1 "Insulin receptor substrate-1 as a signaling molecule for focal adhesion kinase pp125(FAK) and pp60(src)". The Journal of Biological Chemistry 273 (48): 32244–53. November 1998. doi:10.1074/jbc.273.48.32244. PMID 9822703. 
  47. ↑ "Growth hormone stimulates the tyrosine phosphorylation and association of p125 focal adhesion kinase (FAK) with JAK2. Fak is not required for stat-mediated transcription". The Journal of Biological Chemistry 273 (17): 10682–9. April 1998. doi:10.1074/jbc.273.17.10682. PMID 9553131. 
  48. ↑ "Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin". Journal of Immunology 165 (4): 2116–23. August 2000. doi:10.4049/jimmunol.165.4.2116. PMID 10925297. 
  49. ↑ "A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine-phosphorylated". Oncogene 21 (42): 6488–97. September 2002. doi:10.1038/sj.onc.1205840. PMID 12226752. 
  50. ↑ "Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes". The Journal of Experimental Medicine 184 (4): 1365–75. October 1996. doi:10.1084/jem.184.4.1365. PMID 8879209. 
  51. ↑ 51.0 51.1 "Nck-2 interacts with focal adhesion kinase and modulates cell motility". The International Journal of Biochemistry & Cell Biology 34 (7): 791–805. July 2002. doi:10.1016/s1357-2725(02)00002-x. PMID 11950595. 
  52. ↑ "Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae". Molecular and Cellular Biology 16 (7): 3327–37. July 1996. doi:10.1128/mcb.16.7.3327. PMID 8668148. 
  53. ↑ "Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation". Molecular Cell 29 (1): 9–22. January 2008. doi:10.1016/j.molcel.2007.11.031. PMID 18206965. 
  54. ↑ "Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85 alpha with actin filaments and focal adhesion kinase". The Journal of Cell Biology 129 (3): 831–42. May 1995. doi:10.1083/jcb.129.3.831. PMID 7537275. 
  55. ↑ "PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway". The Journal of Biological Chemistry 274 (29): 20693–703. July 1999. doi:10.1074/jbc.274.29.20693. PMID 10400703. 
  56. ↑ "PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow". Oncogene 21 (9): 1450–60. February 2002. doi:10.1038/sj.onc.1205213. PMID 11857088. 
  57. ↑ 57.0 57.1 "Differential regulation of Pyk2 and focal adhesion kinase (FAK). The C-terminal domain of FAK confers response to cell adhesion". The Journal of Biological Chemistry 273 (4): 2384–9. January 1998. doi:10.1074/jbc.273.4.2384. PMID 9442086. 
  58. ↑ 58.0 58.1 "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". The Journal of Biological Chemistry 273 (2): 1003–14. January 1998. doi:10.1074/jbc.273.2.1003. PMID 9422762. 
  59. ↑ "Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy". Molecular Biology of the Cell 12 (8): 2290–307. August 2001. doi:10.1091/mbc.12.8.2290. PMID 11514617. 
  60. ↑ "Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling". The Journal of Cell Biology 145 (4): 851–63. May 1999. doi:10.1083/jcb.145.4.851. PMID 10330411. 
  61. ↑ "A fragment of paxillin binds the alpha 4 integrin cytoplasmic domain (tail) and selectively inhibits alpha 4-mediated cell migration". The Journal of Biological Chemistry 277 (23): 20887–94. June 2002. doi:10.1074/jbc.M110928200. PMID 11919182. 
  62. ↑ "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins". The Journal of Biological Chemistry 272 (11): 7437–44. March 1997. doi:10.1074/jbc.272.11.7437. PMID 9054445. 
  63. ↑ "Identification of LIM3 as the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding". The Journal of Cell Biology 135 (4): 1109–23. November 1996. doi:10.1083/jcb.135.4.1109. PMID 8922390. 
  64. ↑ "Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase". The Journal of Biological Chemistry 273 (41): 26516–21. October 1998. doi:10.1074/jbc.273.41.26516. PMID 9756887. 
  65. ↑ "Cytoskeleton-dependent tyrosine phosphorylation of the p130(Cas) family member HEF1 downstream of the G protein-coupled calcitonin receptor. Calcitonin induces the association of HEF1, paxillin, and focal adhesion kinase". The Journal of Biological Chemistry 274 (35): 25093–8. August 1999. doi:10.1074/jbc.274.35.25093. PMID 10455189. 
  66. ↑ "Suppression of Pyk2 kinase and cellular activities by FIP200". The Journal of Cell Biology 149 (2): 423–30. April 2000. doi:10.1083/jcb.149.2.423. PMID 10769033. 
  67. ↑ "Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion". The Journal of Biological Chemistry 276 (22): 19512–23. June 2001. doi:10.1074/jbc.M009063200. PMID 11278462. 
  68. ↑ "Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples". Cancer Research 62 (9): 2699–707. May 2002. PMID 11980671. 
  69. ↑ "Site-specific phosphorylation of platelet focal adhesion kinase by low-density lipoprotein". The Biochemical Journal 369 (Pt 2): 407–16. January 2003. doi:10.1042/BJ20020410. PMID 12387730. 
  70. ↑ "Relocation of Syk protein-tyrosine kinase to the actin filament network and subsequent association with Fak". European Journal of Biochemistry 248 (3): 827–33. September 1997. doi:10.1111/j.1432-1033.1997.00827.x. PMID 9342235. 
  71. ↑ "Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase". Molecular and Cellular Biology 21 (16): 5332–45. August 2001. doi:10.1128/MCB.21.16.5332-5345.2001. PMID 11463817. 
  72. ↑ "Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin". Journal of Cell Science 112 (2): 181–90. January 1999. doi:10.1242/jcs.112.2.181. PMID 9858471. 
  73. ↑ "Interaction of focal adhesion kinase with cytoskeletal protein talin". The Journal of Biological Chemistry 270 (28): 16995–9. July 1995. doi:10.1074/jbc.270.28.16995. PMID 7622520. 
  74. ↑ "Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth". The Journal of Biological Chemistry 281 (49): 37321–9. December 2006. doi:10.1074/jbc.M605241200. PMID 17043358. 
  75. ↑ "FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis" (in en). FASEB Journal 32 (2): 1099–1107. October 2017. doi:10.1096/fj.201700721r. PMID 29070586. 

Further reading

External links



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