Disease relevance of PTK2

• The replication deficient adenovirus containing the FAK gene (pp125 FAK) was constructed and named Adv-Fak [1].
• To determine whether increased FAK and paxillin protein concentrations are associated with hypertrophy and/or new fiber formation, two additional experiments were performed [2].
• Second, FAK (112% and 611%) and paxillin (87% and 431%) protein concentrations per unit of total protein in the soleus muscle increased at 1 and 8 days after surgical ablation of the synergistic gastrocnemius muscle (a model of hypertrophy without hyperplasia) [2].

High impact information on PTK2

• We propose that pp41/43FRNK functions as an endogenous regulator of pp125FAK, thus providing an unusual means to regulate both tyrosine kinase activity and cellular adhesion to the extracellular matrix [3].
• Src binds to focal adhesion kinase (FAK) through its SH2 domain and subsequently activates it for phosphorylation of downstream substrates [4].
• These data show that Src-mediated phosphorylation of FAK acts as a pivotal regulator of both actin and adhesion dynamics and survival signaling, which, in turn, control apparently distinct processes such as cell migration and anchorage-independent growth [5].
• Expression of 4-9F-FAK in FAK-deficient fibroblasts also disrupts F-actin assembly associated with normal adhesion and spreading [5].
• When ectopically expressed in cells, FRNK has been shown to act as a negative regulator of FAK activity, inhibiting cell spreading, migration, and cell cycle progression [6].

Biological context of PTK2

• A novel protein-tyrosine kinase, designated 'Focal Adhesion Kinase' (FAK), has recently been implicated in signal transduction pathways activated by extracellular adhesion molecules and by neuropeptide growth factors [7].
• The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain [8].
• Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK [8].
• Caspases cleave focal adhesion kinase during apoptosis to generate a FRNK-like polypeptide [9].
• OBJECTIVE: Focal adhesion kinase is implicated in the regulation of cell adhesion, migration, survival, and cell-cycle progression [10].

Anatomical context of PTK2

• Mechanical stimulus was shown to activate focal adhesion kinase (FAK), which specifically became associated with the cytoskeleton after mechanical perturbation, and its association with the cytoskeleton was dependent on tyrosine kinase activity [11].
• We demonstrate that erythroid progenitor cells express several receptor and non-receptor tyrosine kinases, like c-kit, Jak1, Ryk, FAK, Syk, Arg, Csk and members of the insulin receptor family [12].
• METHOD: We generated transgenic mice which overexpressed chicken FAK in vascular endothelial cell under the control of the Tie-2 promoter and enhancer [10].
• These data provide novel evidence that opioid receptor intracellular signaling engages the specific activation of tyrosine kinase FAK and regulates the neuronal cytoskeleton during central nervous system morphogenesis [13].
• Our results show that overexpression of FAK can induce tendon adhesion formation in vivo [1].

Associations of PTK2 with chemical compounds

• We also show that the fibronectin-dependent increase in tyrosine phosphorylation of pp125FAK is accompanied by a concomitant posttranslational modification of p41FRNK [14].
• Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains [8].
• Many cell responses signal through focal adhesion kinase (FAK), often by integrin-induced autophosphorylation of FAK or phosphorylation by Src family kinases [5].
• Immunprecipitation experiments demonstrated that FAK associates with ionotropic glutamate receptors [15].
• Both the phosphotyrosine content and the enzymatic activity of FAK are increased in response to vanadate [16].

Enzymatic interactions of PTK2

• However, pp125FAK is also phosphorylated on tyrosine as a result of integrin stimulation which induces quite different biological consequences including the organisation of focal adhesions when cells spread on fibronectin (reviewed in Schaller and Parsons, 1993) [17].

Other interactions of PTK2

• Moreover, cell spreading during restitution of normal morphology did not require detectable tyrosine phosphorylation of pp125FAK, or its potential substrate paxillin, suggesting that pp125FAK may function more in the turnover of focal adhesions than in their assembly [17].

Analytical, diagnostic and therapeutic context of PTK2

• FAK (77 and 81%) and paxillin (206 and 202%) protein concentrations per unit of total protein in Western blots increased significantly after 1.5 and 7 days, but not after 13 days, of stretch-induced hypertrophy-hyperplasia of the ALD muscle [2].

References