Focal adhesion kinase 1

NameFocal adhesion kinase 1
Synonyms
  • 2.7.10.2
  • FADK 1
  • FAK
  • FAK1
  • Focal adhesion kinase-related nonkinase
  • FRNK
  • p125FAK
  • pp125FAK
  • PPP1R71
  • Protein phosphatase 1 regulatory subunit 71
  • Protein-tyrosine kinase 2
Gene NamePTK2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006032|Focal adhesion kinase 1
MAAAYLDPNLNHTPNSSTKTHLGTGMERSPGAMERVLKVFHYFESNSEPTTWASIIRHGD
ATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHPPEEW
KYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMLEIADQVDQEIALKLGCLEIRRSY
WEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFANLNREESI
LKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNPTHLADFTQVQ
TIQYSNSEDKDRKGMLQLKIAGAPEPLTVTAPSLTIAENMADLIDGYCRLVNGTSQSFII
RPQKEGERALPSIPKLANSEKQGMRTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRE
RIELGRCIGEGQFGDVHQGIYMSPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDH
PHIVKLIGVITENPVWIIMELCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESK
RFVHRDIAARNVLVSSNDCVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFT
SASDVWMFGVCMWEILMHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWA
YDPSRRPRFTELKAQLSTILEEEKAQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGY
PSPRSSEGFYPSPQHMVQTNHYQVSGYPGSHGITAMAGSIYPGQASLLDQTDSWNHRPQE
IAMWQPNVEDSTVLDLRGIGQVLPTHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLS
RGSIDREDGSLQGPIGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLGSLASLSSPADSYNE
GVKLQPQEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLA
LRTLLATVDETIPLLPASTHREIEMAQKLLNSDLGELINKMKLAQQYVMTSLQQEYKKQM
LTAAHALAVDAKNLLDVIDQARLKMLGQTRPH
Number of residues1052
Molecular Weight119232.025
Theoretical pI6.61
GO Classification
Functions
  • non-membrane spanning protein tyrosine kinase activity
  • JUN kinase binding
  • protein kinase binding
  • signal transducer activity
  • actin binding
  • ATP binding
  • protein kinase activity
  • SH2 domain binding
  • protein tyrosine kinase activity
  • receptor binding
Processes
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • establishment of cell polarity
  • neuron migration
  • Ras protein signal transduction
  • innate immune response
  • regulation of focal adhesion assembly
  • small GTPase mediated signal transduction
  • heart morphogenesis
  • vascular endothelial growth factor receptor signaling pathway
  • peptidyl-tyrosine autophosphorylation
  • regulation of cell shape
  • regulation of osteoblast differentiation
  • positive regulation of cell proliferation
  • peptidyl-tyrosine phosphorylation
  • regulation of cell adhesion mediated by integrin
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • positive regulation of protein phosphorylation
  • negative regulation of organ growth
  • cell motility
  • integrin-mediated signaling pathway
  • regulation of cell proliferation
  • regulation of protein phosphorylation
  • platelet activation
  • vasculogenesis
  • angiogenesis
  • Fc-epsilon receptor signaling pathway
  • negative regulation of cell-cell adhesion
  • regulation of GTPase activity
  • cytoskeleton organization
  • extracellular matrix organization
  • regulation of endothelial cell migration
  • positive regulation of protein kinase activity
  • positive regulation of cell migration
  • negative regulation of synapse assembly
  • placenta development
  • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
  • positive regulation of phosphatidylinositol 3-kinase activity
  • activation of MAPKK activity
  • central nervous system neuron axonogenesis
  • regulation of cytoskeleton organization
  • protein autophosphorylation
  • cell adhesion
  • ephrin receptor signaling pathway
  • apoptotic process
  • establishment of nucleus localization
  • cellular component disassembly involved in execution phase of apoptosis
  • transforming growth factor beta receptor signaling pathway
  • growth hormone receptor signaling pathway
  • fibroblast growth factor receptor signaling pathway
  • netrin-activated signaling pathway
  • axon guidance
  • microtubule cytoskeleton organization
  • signal complex assembly
  • blood coagulation
  • positive regulation of protein kinase B signaling
  • insulin receptor signaling pathway
  • regulation of epithelial cell migration
  • cell differentiation
  • embryo development
  • endothelial cell migration
  • MAPK cascade
  • regulation of substrate adhesion-dependent cell spreading
  • cell migration
  • negative regulation of anoikis
  • negative regulation of apoptotic process
  • epidermal growth factor receptor signaling pathway
  • negative regulation of axonogenesis
  • programmed cell death
  • neurotrophin TRK receptor signaling pathway
Components
  • plasma membrane
  • stress fiber
  • lamellipodium
  • apical plasma membrane
  • cytoplasm
  • focal adhesion
  • cytosol
  • extrinsic component of cytoplasmic side of plasma membrane
  • cytoskeleton
  • nucleus
  • microtubule organizing center
  • cell cortex
General FunctionSignal transducer activity
Specific FunctionNon-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ05397
UniProtKB Entry NameFAK1_HUMAN
Cellular LocationCell junction
Gene sequence
>lcl|BSEQ0021683|Focal adhesion kinase 1 (PTK2)
ATGGCAGCTGCTTACCTTGACCCCAACTTGAATCACACACCAAATTCGAGTACTAAGACT
CACCTGGGTACTGGTATGGAACGTTCTCCTGGTGCAATGGAGCGAGTATTAAAGGTCTTT
CATTATTTTGAAAGCAATAGTGAGCCAACCACCTGGGCCAGTATTATCAGGCATGGAGAT
GCTACTGATGTCAGGGGCATCATTCAGAAGATAGTGGACAGTCACAAAGTAAAGCATGTG
GCCTGCTATGGATTCCGCCTCAGTCACCTGCGGTCAGAGGAGGTTCACTGGCTTCACGTG
GATATGGGCGTCTCCAGTGTGAGGGAGAAGTATGAGCTTGCTCACCCACCAGAGGAGTGG
AAATATGAATTGAGAATTCGTTATTTGCCAAAAGGATTTCTAAACCAGTTTACTGAAGAT
AAGCCAACTTTGAATTTCTTCTATCAACAGGTGAAGAGCGATTATATGTTAGAGATAGCT
GATCAAGTGGACCAGGAAATTGCTTTGAAGTTGGGTTGTCTAGAAATACGGCGATCATAC
TGGGAGATGCGGGGCAATGCACTAGAAAAGAAGTCTAACTATGAAGTATTAGAAAAAGAT
GTTGGTTTAAAGCGATTTTTTCCTAAGAGTTTACTGGATTCTGTCAAGGCCAAAACACTA
AGAAAACTGATCCAACAAACATTTAGACAATTTGCCAACCTTAATAGAGAAGAAAGTATT
CTGAAATTCTTTGAGATCCTGTCTCCAGTCTACAGATTTGATAAGGAATGCTTCAAGTGT
GCTCTTGGTTCAAGCTGGATTATTTCAGTGGAACTGGCAATCGGCCCAGAAGAAGGAATC
AGTTACCTAACGGACAAGGGCTGCAATCCCACACATCTTGCTGACTTCACTCAAGTGCAA
ACCATTCAGTATTCAAACAGTGAAGACAAGGACAGAAAAGGAATGCTACAACTAAAAATA
GCAGGTGCACCCGAGCCTCTGACAGTGACGGCACCATCCCTAACCATTGCGGAGAATATG
GCTGACCTAATAGATGGGTACTGCCGGCTGGTGAATGGAACCTCGCAGTCATTTATCATC
AGACCTCAGAAAGAAGGTGAACGGGCTTTGCCATCAATACCAAAGTTGGCCAACAGCGAA
AAGCAAGGCATGCGGACACACGCCGTCTCTGTGTCAGAAACAGATGATTATGCTGAGATT
ATAGATGAAGAAGATACTTACACCATGCCCTCAACCAGGGATTATGAGATTCAAAGAGAA
AGAATAGAACTTGGACGATGTATTGGAGAAGGCCAATTTGGAGATGTACATCAAGGCATT
TATATGAGTCCAGAGAATCCAGCTTTGGCGGTTGCAATTAAAACATGTAAAAACTGTACT
TCGGACAGCGTGAGAGAGAAATTTCTTCAAGAAGCCTTAACAATGCGTCAGTTTGACCAT
CCTCATATTGTGAAGCTGATTGGAGTCATCACAGAGAATCCTGTCTGGATAATCATGGAG
CTGTGCACACTTGGAGAGCTGAGGTCATTTTTGCAAGTAAGGAAATACAGTTTGGATCTA
GCATCTTTGATCCTGTATGCCTATCAGCTTAGTACAGCTCTTGCATATCTAGAGAGCAAA
AGATTTGTACACAGGGACATTGCTGCTCGGAATGTTCTGGTGTCCTCAAATGATTGTGTA
AAATTAGGAGACTTTGGATTATCCCGATATATGGAAGATAGTACTTACTACAAAGCTTCC
AAAGGAAAATTGCCTATTAAATGGATGGCTCCAGAGTCAATCAATTTTCGACGTTTTACC
TCAGCTAGTGACGTATGGATGTTTGGTGTGTGTATGTGGGAGATACTGATGCATGGTGTG
AAGCCTTTTCAAGGAGTGAAGAACAATGATGTAATCGGTCGAATTGAAAATGGGGAAAGA
TTACCAATGCCTCCAAATTGTCCTCCTACCCTCTACAGCCTTATGACGAAATGCTGGGCC
TATGACCCCAGCAGGCGGCCCAGGTTTACTGAACTTAAAGCTCAGCTCAGCACAATCCTG
GAGGAAGAGAAGGCTCAGCAAGAAGAGCGCATGAGGATGGAGTCCAGAAGACAGGCCACA
GTGTCCTGGGACTCCGGAGGGTCTGATGAAGCACCGCCCAAGCCCAGCAGACCGGGTTAT
CCCAGTCCGAGGTCCAGCGAAGGATTTTATCCCAGCCCACAGCACATGGTACAAACCAAT
CATTACCAGGTTTCTGGCTACCCTGGTTCACATGGAATCACAGCCATGGCTGGCAGCATC
TATCCAGGTCAGGCATCTCTTTTGGACCAAACAGATTCATGGAATCATAGACCTCAGGAG
ATAGCAATGTGGCAGCCCAATGTGGAGGACTCTACAGTATTGGACCTGCGAGGGATTGGG
CAAGTGTTGCCAACCCATCTGATGGAAGAGCGTCTAATCCGACAGCAACAGGAAATGGAA
GAAGATCAGCGCTGGCTGGAAAAAGAGGAAAGATTTCTGAAACCTGATGTGAGACTCTCT
CGAGGCAGTATTGACAGGGAGGATGGAAGTCTTCAGGGTCCGATTGGAAACCAACATATA
TATCAGCCTGTGGGTAAACCAGGTAAAGAAGAAAAGAATTGGGCGGAAAGAAATCCTGCA
GCTCCACCAAAGAAACCGCCTCGCCCTGGAGCTCCCGGTCATCTGGGAAGCCTTGCCAGC
CTCAGCAGCCCTGCTGACAGCTACAACGAGGGTGTCAAGCCATGGAGGCTTCAGCCCCAG
GAAATCAGCCCCCCTCCTACTGCCAACCTGGACCGGTCGAATGATAAGGTGTACGAGAAT
GTGACGGGCCTGGTGAAAGCTGTCATCGAGATGTCCAGTAAAATCCAGCCAGCCCCACCA
GAGGAGTATGTCCCTATGGTGAAGGAAGTCGGCTTGGCCCTGAGGACATTATTGGCCACT
GTGGATGAGACCATTCCCCTCCTACCAGCCAGCACCCACCGAGAGATTGAGATGGCACAG
AAGCTATTGAACTCTGACCTGGGTGAGCTCATCAACAAGATGAAACTGGCCCAGCAGTAT
GTCATGACCAGCCTCCAGCAAGAGTACAAAAAGCAAATGCTGACTGCTGCTCACGCCCTG
GCTGTGGATGCCAAAAACTTACTCGATGTCATTGACCAAGCAAGACTGAAAATGCTTGGG
CAGACGAGACCACACTGA
GenBank Gene IDL13616
GeneCard IDNot Available
GenAtlas IDPTK2
HGNC IDHGNC:9611
Chromosome Location8
Locus8q24-qter
References
  1. Whitney GS, Chan PY, Blake J, Cosand WL, Neubauer MG, Aruffo A, Kanner SB: Human T and B lymphocytes express a structurally conserved focal adhesion kinase, pp125FAK. DNA Cell Biol. 1993 Nov;12(9):823-30. 7692878
  2. Andre E, Becker-Andre M: Expression of an N-terminally truncated form of human focal adhesion kinase in brain. Biochem Biophys Res Commun. 1993 Jan 15;190(1):140-7. 8422239
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. 16421571
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. Lee ST, Strunk KM, Spritz RA: A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene. 1993 Dec;8(12):3403-10. 8247543
  7. Matsuya M, Sasaki H, Aoto H, Mitaka T, Nagura K, Ohba T, Ishino M, Takahashi S, Suzuki R, Sasaki T: Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions. J Biol Chem. 1998 Jan 9;273(2):1003-14. 9422762
  8. Fujita H, Kamiguchi K, Cho D, Shibanuma M, Morimoto C, Tachibana K: Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase. J Biol Chem. 1998 Oct 9;273(41):26516-21. 9756887
  9. Miao H, Burnett E, Kinch M, Simon E, Wang B: Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol. 2000 Feb;2(2):62-9. 10655584
  10. Chen R, Kim O, Li M, Xiong X, Guan JL, Kung HJ, Chen H, Shimizu Y, Qiu Y: Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nat Cell Biol. 2001 May;3(5):439-44. 11331870
  11. Hecker TP, Grammer JR, Gillespie GY, Stewart J Jr, Gladson CL: Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples. Cancer Res. 2002 May 1;62(9):2699-707. 11980671
  12. Abbi S, Ueda H, Zheng C, Cooper LA, Zhao J, Christopher R, Guan JL: Regulation of focal adhesion kinase by a novel protein inhibitor FIP200. Mol Biol Cell. 2002 Sep;13(9):3178-91. 12221124
  13. Relou IA, Bax LA, van Rijn HJ, Akkerman JW: Site-specific phosphorylation of platelet focal adhesion kinase by low-density lipoprotein. Biochem J. 2003 Jan 15;369(Pt 2):407-16. 12387730
  14. Xia H, Nho RS, Kahm J, Kleidon J, Henke CA: Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in regulating fibroblast survival in response to contraction of type I collagen matrices via a beta 1 integrin viability signaling pathway. J Biol Chem. 2004 Jul 30;279(31):33024-34. Epub 2004 May 27. 15166238
  15. Continolo S, Baruzzi A, Majeed M, Caveggion E, Fumagalli L, Lowell CA, Berton G: The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization. Exp Cell Res. 2005 Jan 15;302(2):253-69. 15561106
  16. Golubovskaya VM, Finch R, Cance WG: Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53. J Biol Chem. 2005 Jul 1;280(26):25008-21. Epub 2005 Apr 25. 15855171
  17. Ezratty EJ, Partridge MA, Gundersen GG: Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol. 2005 Jun;7(6):581-90. Epub 2005 May 15. 15895076
  18. Garces CA, Kurenova EV, Golubovskaya VM, Cance WG: Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells. Cancer Res. 2006 Feb 1;66(3):1446-54. 16452200
  19. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  20. Nagoshi Y, Yamamoto G, Irie T, Tachikawa T: Expression of FAK-related non-kinase (FRNK) coincides with morphological change in the early stage of cell adhesion. Med Mol Morphol. 2006 Sep;39(3):154-60. 16998626
  21. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. 16964243
  22. Halder J, Lin YG, Merritt WM, Spannuth WA, Nick AM, Honda T, Kamat AA, Han LY, Kim TJ, Lu C, Tari AM, Bornmann W, Fernandez A, Lopez-Berestein G, Sood AK: Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res. 2007 Nov 15;67(22):10976-83. 18006843
  23. Slack-Davis JK, Martin KH, Tilghman RW, Iwanicki M, Ung EJ, Autry C, Luzzio MJ, Cooper B, Kath JC, Roberts WG, Parsons JT: Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar 28. 17395594
  24. Salasznyk RM, Klees RF, Boskey A, Plopper GE: Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5. J Cell Biochem. 2007 Feb 1;100(2):499-514. 16927379
  25. Liu TJ, LaFortune T, Honda T, Ohmori O, Hatakeyama S, Meyer T, Jackson D, de Groot J, Yung WK: Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther. 2007 Apr;6(4):1357-67. 17431114
  26. Sundberg-Smith LJ, DiMichele LA, Sayers RL, Mack CP, Taylor JM: The LIM protein leupaxin is enriched in smooth muscle and functions as an serum response factor cofactor to induce smooth muscle cell gene transcription. Circ Res. 2008 Jun 20;102(12):1502-11. doi: 10.1161/CIRCRESAHA.107.170357. Epub 2008 May 22. 18497331
  27. Semaan N, Alsaleh G, Gottenberg JE, Wachsmann D, Sibilia J: Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways. J Immunol. 2008 Mar 1;180(5):3485-91. 18292575
  28. Singh MK, Dadke D, Nicolas E, Serebriiskii IG, Apostolou S, Canutescu A, Egleston BL, Golemis EA: A novel Cas family member, HEPL, regulates FAK and cell spreading. Mol Biol Cell. 2008 Apr;19(4):1627-36. doi: 10.1091/mbc.E07-09-0953. Epub 2008 Feb 6. 18256281
  29. Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D: Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell. 2008 Jan 18;29(1):9-22. doi: 10.1016/j.molcel.2007.11.031. 18206965
  30. Le Romancer M, Treilleux I, Leconte N, Robin-Lespinasse Y, Sentis S, Bouchekioua-Bouzaghou K, Goddard S, Gobert-Gosse S, Corbo L: Regulation of estrogen rapid signaling through arginine methylation by PRMT1. Mol Cell. 2008 Jul 25;31(2):212-21. doi: 10.1016/j.molcel.2008.05.025. 18657504
  31. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  32. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  33. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  34. Oh MA, Choi S, Lee MJ, Choi MC, Lee SA, Ko W, Cance WG, Oh ES, Buday L, Kim SH, Lee JW: Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes. Biochim Biophys Acta. 2009 May;1793(5):781-91. doi: 10.1016/j.bbamcr.2009.01.015. Epub 2009 Feb 5. 19339212
  35. Sachdev S, Bu Y, Gelman IH: Paxillin-Y118 phosphorylation contributes to the control of Src-induced anchorage-independent growth by FAK and adhesion. BMC Cancer. 2009 Jan 12;9:12. doi: 10.1186/1471-2407-9-12. 19138410
  36. Tamura T, Chiba J: STEAP4 regulates focal adhesion kinase activation and CpG motifs within STEAP4 promoter region are frequently methylated in DU145, human androgen-independent prostate cancer cells. Int J Mol Med. 2009 Nov;24(5):599-604. 19787193
  37. Morales SA, Mareninov S, Coulam P, Wadehra M, Goodglick L, Braun J, Gordon LK: Functional consequences of interactions between FAK and epithelial membrane protein 2 (EMP2). Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4949-56. doi: 10.1167/iovs.08-3315. Epub 2009 Jun 3. 19494199
  38. Pylayeva Y, Gillen KM, Gerald W, Beggs HE, Reichardt LF, Giancotti FG: Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J Clin Invest. 2009 Feb;119(2):252-66. doi: 10.1172/JCI37160. Epub 2009 Jan 19. 19147981
  39. Yamazaki T, Masuda J, Omori T, Usui R, Akiyama H, Maru Y: EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility. J Cell Sci. 2009 Jan 15;122(Pt 2):243-55. doi: 10.1242/jcs.036467. 19118217
  40. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  41. Sun H, Pisle S, Gardner ER, Figg WD: Bioluminescent imaging study: FAK inhibitor, PF-562,271, preclinical study in PC3M-luc-C6 local implant and metastasis xenograft models. Cancer Biol Ther. 2010 Jul 1;10(1):38-43. Epub 2010 Jul 9. 20495381
  42. Tanaka T, Moriwaki K, Murata S, Miyasaka M: LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and suppresses the integrin-induced tyrosine phosphorylation of paxillin. Cancer Sci. 2010 Feb;101(2):363-8. doi: 10.1111/j.1349-7006.2009.01398.x. Epub 2009 Oct 12. 19917054
  43. Cai GQ, Zheng A, Tang Q, White ES, Chou CF, Gladson CL, Olman MA, Ding Q: Downregulation of FAK-related non-kinase mediates the migratory phenotype of human fibrotic lung fibroblasts. Exp Cell Res. 2010 May 15;316(9):1600-9. doi: 10.1016/j.yexcr.2010.01.021. Epub 2010 Jan 25. 20109444
  44. Nagano M, Hoshino D, Sakamoto T, Kawasaki N, Koshikawa N, Seiki M: ZF21 protein regulates cell adhesion and motility. J Biol Chem. 2010 Jul 2;285(27):21013-22. doi: 10.1074/jbc.M110.106443. Epub 2010 May 3. 20439989
  45. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ: CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010 Feb;11(2):155-61. doi: 10.1038/ni.1836. Epub 2009 Dec 27. 20037584
  46. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  47. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  48. Plaza-Menacho I, Morandi A, Mologni L, Boender P, Gambacorti-Passerini C, Magee AI, Hofstra RM, Knowles P, McDonald NQ, Isacke CM: Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism. J Biol Chem. 2011 May 13;286(19):17292-302. doi: 10.1074/jbc.M110.168500. Epub 2011 Mar 22. 21454698
  49. Armacki M, Joodi G, Nimmagadda SC, de Kimpe L, Pusapati GV, Vandoninck S, Van Lint J, Illing A, Seufferlein T: A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis. Oncogene. 2014 Feb 27;33(9):1167-80. doi: 10.1038/onc.2013.43. Epub 2013 Mar 18. 23503467
  50. Schlaepfer DD, Hauck CR, Sieg DJ: Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71(3-4):435-78. 10354709
  51. Nikolopoulos SN, Giancotti FG: Netrin-integrin signaling in epithelial morphogenesis, axon guidance and vascular patterning. Cell Cycle. 2005 Mar;4(3):e131-5. Epub 2005 Mar 18. 15725728
  52. Mitra SK, Schlaepfer DD: Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol. 2006 Oct;18(5):516-23. Epub 2006 Aug 17. 16919435
  53. Vadali K, Cai X, Schaller MD: Focal adhesion kinase: an essential kinase in the regulation of cardiovascular functions. IUBMB Life. 2007 Nov;59(11):709-16. 17968709
  54. Lim ST, Mikolon D, Stupack DG, Schlaepfer DD: FERM control of FAK function: implications for cancer therapy. Cell Cycle. 2008 Aug;7(15):2306-14. Epub 2008 May 29. 18677107
  55. Tomar A, Schlaepfer DD: Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility. Curr Opin Cell Biol. 2009 Oct;21(5):676-83. doi: 10.1016/j.ceb.2009.05.006. Epub 2009 Jun 12. 19525103
  56. Golubovskaya VM, Kweh FA, Cance WG: Focal adhesion kinase and cancer. Histol Histopathol. 2009 Apr;24(4):503-10. 19224453
  57. Golubovskaya VM, Cance W: Focal adhesion kinase and p53 signal transduction pathways in cancer. Front Biosci (Landmark Ed). 2010 Jun 1;15:901-12. 20515733
  58. Chatzizacharias NA, Kouraklis GP, Theocharis SE: The role of focal adhesion kinase in early development. Histol Histopathol. 2010 Aug;25(8):1039-55. 20552554
  59. Guan JL: Integrin signaling through FAK in the regulation of mammary stem cells and breast cancer. IUBMB Life. 2010 Apr;62(4):268-76. doi: 10.1002/iub.303. 20101634
  60. Schaller MD: Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010 Apr 1;123(Pt 7):1007-13. doi: 10.1242/jcs.045112. 20332118
  61. Hall JE, Fu W, Schaller MD: Focal adhesion kinase: exploring Fak structure to gain insight into function. Int Rev Cell Mol Biol. 2011;288:185-225. doi: 10.1016/B978-0-12-386041-5.00005-4. 21482413
  62. Zhu M, Settele F, Kotak S, Sanchez-Pulido L, Ehret L, Ponting CP, Gonczy P, Hoffmann I: MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression. J Cell Biol. 2013 Mar 18;200(6):773-87. doi: 10.1083/jcb.201207050. 23509069
  63. Arold ST, Hoellerer MK, Noble ME: The structural basis of localization and signaling by the focal adhesion targeting domain. Structure. 2002 Mar;10(3):319-27. 12005431
  64. Nowakowski J, Cronin CN, McRee DE, Knuth MW, Nelson CG, Pavletich NP, Rogers J, Sang BC, Scheibe DN, Swanson RV, Thompson DA: Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure. 2002 Dec;10(12):1659-67. 12467573
  65. Hoellerer MK, Noble ME, Labesse G, Campbell ID, Werner JM, Arold ST: Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain. Structure. 2003 Oct;11(10):1207-17. 14527389
  66. Roberts WG, Ung E, Whalen P, Cooper B, Hulford C, Autry C, Richter D, Emerson E, Lin J, Kath J, Coleman K, Yao L, Martinez-Alsina L, Lorenzen M, Berliner M, Luzzio M, Patel N, Schmitt E, LaGreca S, Jani J, Wessel M, Marr E, Griffor M, Vajdos F: Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res. 2008 Mar 15;68(6):1935-44. doi: 10.1158/0008-5472.CAN-07-5155. 18339875
  67. Garron ML, Arthos J, Guichou JF, McNally J, Cicala C, Arold ST: Structural basis for the interaction between focal adhesion kinase and CD4. J Mol Biol. 2008 Feb 1;375(5):1320-8. Epub 2007 Nov 22. 18078954
  68. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846