PMID- 10373530
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Jul
TI  - Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell
      spreading and migration requiring both auto- and activation loop phosphorylation 
      sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2.
PG  - 4806-18
AB  - Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in 
      integrin-mediated control of cell behavior. Following cell adhesion to components
      of the extracellular matrix, FAK becomes phosphorylated at multiple sites,
      including tyrosines 397, 576, and 577. Tyr-397 is an autophosphorylation site
      that promotes interaction with c-Src or Fyn. Tyr-576 and Tyr-577 lie in the
      putative activation loop of the kinase domain, and FAK catalytic activity may be 
      elevated through phosphorylation of these residues by associated Src family
      kinase. Recent studies have implicated FAK as a positive regulator of cell
      spreading and migration. To further study the mechanism of adhesion-induced FAK
      activation and the possible role and signaling requirements for FAK in cell
      spreading and migration, we utilized the tetracycline repression system to
      achieve inducible expression of either wild-type FAK or phosphorylation site
      mutants in fibroblasts derived from FAK-null mouse embryos. Using these Tet-FAK
      cells, we demonstrated that both the FAK autophosphorylation and activation loop 
      sites are critical for maximum adhesion-induced FAK activation and FAK-enhanced
      cell spreading and migration responses. Negative effects on cell spreading and
      migration, as well as decreased phosphorylation of the substrate p130(Cas), were 
      observed upon induced expression of the FAK autophosphorylation site mutant.
      These negative effects appear to result from an inhibition of integrin-mediated
      signaling by the FAK-related kinase Pyk2/CAKbeta/RAFTK/CadTK.
FAU - Owen, J D
AU  - Owen JD
AD  - Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, 
      Tennessee 37232, USA.
FAU - Ruest, P J
AU  - Ruest PJ
FAU - Fry, D W
AU  - Fry DW
FAU - Hanks, S K
AU  - Hanks SK
LA  - eng
GR  - F31 AA005408/AA/NIAAA NIH HHS/United States
GR  - R01 GM049882/GM/NIGMS NIH HHS/United States
GR  - T32 CA078136/CA/NCI NIH HHS/United States
GR  - F31-AA05408/AA/NIAAA NIH HHS/United States
GR  - T32-CA78136/CA/NCI NIH HHS/United States
GR  - R01-GM49882/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Bcar1 protein, mouse)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Crk-Associated Substrate Protein)
RN  - 0 (Fibronectins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Retinoblastoma-Like Protein p130)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Ptk2 protein, mouse)
RN  - EC 2.7.10.2 (Ptk2b protein, mouse)
RN  - F8VB5M810T (Tetracycline)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Binding Sites
MH  - Catalysis
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/biosynthesis/genetics/*physiology
MH  - Cell Movement/*physiology
MH  - Crk-Associated Substrate Protein
MH  - Fibronectins/metabolism
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Kinase 2
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Gene Expression
MH  - Mice
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/biosynthesis/genetics/*metabolism/*physiology
MH  - *Proteins
MH  - Rabbits
MH  - Retinoblastoma-Like Protein p130
MH  - Tetracycline/pharmacology
MH  - Time Factors
MH  - Tyrosine/*metabolism
MH  - Up-Regulation
PMC - PMC84279
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1128/mcb.19.7.4806 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jul;19(7):4806-18. doi: 10.1128/mcb.19.7.4806.