PMID:9545257

Citation	Li, X, Hunter, D, Morris, J, Haskill, JS and Earp, HS (1998) A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation by a two-stage process involving adherence and a subsequent intracellular signal. J. Biol. Chem. 273:9361-4
Abstract	Freshly isolated human monocytes do not express p125(FAK) but upon adherence to substrata activate the highly related calcium-dependent tyrosine kinase (CADTK), also known as Pyk2, CAKbeta, RAFTK, and FAK2. The monocyte CADTK was 5 kDa smaller than protein from epithelial cells; isolation and sequencing of the monocyte CADTK cDNA revealed a predicted 42-amino acid deletion between the two proline-rich domains of the enzyme. The nucleic acid sequence suggests that the deletion is caused by alternative RNA splicing. This species was also found in T and B lymphocytes and appears to be the predominant form of cytoskeletal associated tyrosine kinase in non-neoplastic, circulating, hematopoietic cells. CADTK was not activated when monocytes maintained in suspension were treated with agents that produce an intracellular calcium (thapsigargin) or protein kinase C (phorbol 12-myristate 13-acetate) signal including a chemokine, RANTES, that binds to the HIV co-receptor, CCK5. In contrast, monocyte adherence to tissue culture plastic-stimulated CADTK tyrosine phosphorylation, a process that was enhanced by thapsigargin, phorbol 12-myristate 13-acetate, and RANTES but that was completely blocked by preincubation with cytochalasin D. When compared with plastic, adherence to fibronectin- or collagen-coated surfaces produced only minimal CADTK activation but permitted significant stimulation by added thapsigargin. These data suggest that in a cell type that lacks p125(FAK), CADTK plays an early role in post-adherence signaling. Its activation involves two stages, cytoskeletal engagement, which is permissive, and co-stimulatory signals (calcium or protein kinase C) generated by extensive cell surface engagement, agonists, or inflammatory chemokines.
Links	PubMed
Keywords	Alternative Splicing; Amino Acid Sequence; Calcium/metabolism; Cell Adhesion Molecules/blood; Cell Line; Cells, Cultured; Chemokine CCL5/pharmacology; Focal Adhesion Kinase 1; Focal Adhesion Kinase 2; Focal Adhesion Protein-Tyrosine Kinases; Genetic Variation; Humans; Isoenzymes/biosynthesis; Isoenzymes/chemistry; Isoenzymes/genetics; Jurkat Cells; Molecular Sequence Data; Monocytes/enzymology; Polymerase Chain Reaction; Protein Kinase C/metabolism; Protein-Tyrosine Kinases/biosynthesis; Protein-Tyrosine Kinases/blood; Protein-Tyrosine Kinases/chemistry; Protein-Tyrosine Kinases/genetics; T-Lymphocytes/enzymology; Tetradecanoylphorbol Acetate/pharmacology; Thapsigargin/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FAK2		GO:0038083: peptidyl-tyrosine autophosphorylation	ECO:0000314:		P		Figure 5	complete CACAO 9303
HUMAN:FAK2	involved_in	GO:0038083: peptidyl-tyrosine autophosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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