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Gene Review

PTK7  -  protein tyrosine kinase 7 (inactive)

Homo sapiens

Synonyms: CCK-4, CCK4, Colon carcinoma kinase 4, Inactive tyrosine-protein kinase 7, Protein-tyrosine kinase 7, ...
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Disease relevance of PTK7


Psychiatry related information on PTK7


High impact information on PTK7

  • The smaller isoforms CCK-8 and CCK-4 are rapidly taken up into hepatocytes, metabolized, and excreted into bile [9].
  • BACKGROUND: We investigated whether the selective brain cholecystokinin (CCKB) receptor antagonist, L-365,260, could antagonize the panicogenic effects of CCK-tetrapeptide (CCK-4) in patients with panic disorder [5].
  • CONCLUSION: These data suggest that CCKB receptors are an important site of action of exogenous CCK-4 [5].
  • Patients (N = 29) received a single oral dose of L-365,260 (10 or 50 mg) or placebo 90 minutes prior to injection of CCK-4 [5].
  • Increases in heart rate following CCK-4 injection were markedly reduced with both the 50-mg (P < .0001) and 10-mg (P < .01) doses compared with placebo [5].

Chemical compound and disease context of PTK7


Biological context of PTK7


Anatomical context of PTK7


Associations of PTK7 with chemical compounds

  • The 1,070 amino acid PTK7 polypeptide deduced from the cDNA sequence constitutes receptor protein tyrosine kinase (RPTK), but has several unusual residues in some of the highly conserved tyrosine kinase motifs [1].
  • Using sedimentation equilibrium in C14 betaine micelles, we discovered that the CCK4 TMD is unable to drive strong protein-protein interactions [18].
  • The biologically active conformation for CCK-4 and the little gastrin hexapeptide has also been deduced [19].
  • Pentagastrin provides a readily available alternative to CCK4 for studying the CCK receptor system and exploring its involvement in human anxiety [20].
  • While these findings suggest that at least part of the neuroendocrine action of CCK-4 is mediated through the 5-HT system, the locus of the 5-HT-CCK interaction and the specific 5-HT receptor subtype involved remains to be determined [21].

Regulatory relationships of PTK7

  • The patients without CCK-4-induced attacks had a brief but less pronounced increase in ACTH concentrations [22].
  • CCK-B antagonists suppressed CCK-4-induced calcium mobilization more potently than CCK-A antagonist [15].
  • Other articles describe the interaction between a 5HT(3) antagonist and CCK-induced satiety and c-fos activation and document secretion of oxytocin and vasopressin in female patients and controls in response to CCK 4 administration.There is good reason to believe that the future is bright for research on CCK [23].

Other interactions of PTK7

  • Novel candidate oncogenes included dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2) and protein tyrosine kinase 7 (PTK7) [24].
  • The CCK receptor agonist, CCK-tetrapeptide (CCK-4) fulfills criteria for a panicogenic agent and there is evidence that PD might be associated with an abnormal function of the CCK system [25].
  • ACTH secretion was significantly higher in the patients with CCK-4-induced panic attacks than in those without such attacks [22].
  • CCK-A receptors have high affinity for sulphated CCK-8 and for MK-329 but low affinity for desulphated CCK-8 and CCK-4 whilst CCK-B sites bind MK-329 with low affinity and discriminate poorly between sulphated and desulphated CCK-8 [26].
  • These major differences in preferred structures between the common CCK-7/CER-7 peptides and the common CCK-4/little gastrin peptides explain the mutually exclusive activities of these two sets of peptides [19].

Analytical, diagnostic and therapeutic context of PTK7


  1. Characterization of the human full-length PTK7 cDNA encoding a receptor protein tyrosine kinase-like molecule closely related to chick KLG. Park, S.K., Lee, H.S., Lee, S.T. J. Biochem. (1996) [Pubmed]
  2. Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma. Easty, D.J., Mitchell, P.J., Patel, K., Flørenes, V.A., Spritz, R.A., Bennett, D.C. Int. J. Cancer (1997) [Pubmed]
  3. The ventilatory response to cholecystokinin tetrapeptide in healthy volunteers. Katzman, M.A., Duffin, J., Shlik, J., Bradwejn, J. Neuropsychopharmacology (2002) [Pubmed]
  4. Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects. Gunnarsson, T., Eklundh, T., Eriksson, M., Qureshi, G.A., Sjöberg, S., Nordin, C. Regul. Pept. (1997) [Pubmed]
  5. The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder. Bradwejn, J., Koszycki, D., Couëtoux du Tertre, A., van Megen, H., den Boer, J., Westenberg, H. Arch. Gen. Psychiatry (1994) [Pubmed]
  6. Decrease in short-term memory function induced by CCK-4 in healthy volunteers. Shlik, J., Koszycki, D., Bradwejn, J. Peptides (1998) [Pubmed]
  7. Relationship between SCL-90, Maudsley Personality Inventory and CCK4-induced intracellular calcium response in T cells. Akiyoshi, J., Yamauchi, C., Furuta, M., Katsuragi, S., Kohno, Y., Yamamoto, Y., Miyamoto, M., Tsutsumi, T., Isogawa, K., Fujii, I. Psychiatry research. (1998) [Pubmed]
  8. Effects of CCK-tetrapeptide in patients with social phobia and obsessive-compulsive disorder. Katzman, M.A., Koszycki, D., Bradwejn, J. Depression and anxiety. (2004) [Pubmed]
  9. Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver. Ismair, M.G., Stieger, B., Cattori, V., Hagenbuch, B., Fried, M., Meier, P.J., Kullak-Ublick, G.A. Gastroenterology (2001) [Pubmed]
  10. Effect of the selective serotonin reuptake inhibitor fluvoxamine on CCK-4 induced panic attacks. van Megen, H.J., Westenberg, H.G., den Boer, J.A., Slaap, B., Scheepmakers, A. Psychopharmacology (Berl.) (1997) [Pubmed]
  11. Megestrol attenuates the hormonal response to CCK-4-induced panic attacks. Raedler, T.J., Jahn, H., Goedeken, B., Gescher, D.M., Kellner, M., Wiedemann, K. Depression and anxiety. (2006) [Pubmed]
  12. Assignment of PTK7 encoding a receptor protein tyrosine kinase-like molecule to human chromosome 6p21.1-->p12.2 by fluorescence in situ hybridization. Banga, S.S., Ozer, H.L., Park, S.K., Lee, S.T. Cytogenet. Cell Genet. (1997) [Pubmed]
  13. Organization of the human PTK7 gene encoding a receptor protein tyrosine kinase-like molecule and alternative splicing of its mRNA. Jung, J.W., Ji, A.R., Lee, J., Kim, U.J., Lee, S.T. Biochim. Biophys. Acta (2002) [Pubmed]
  14. Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Mossie, K., Jallal, B., Alves, F., Sures, I., Plowman, G.D., Ullrich, A. Oncogene (1995) [Pubmed]
  15. CCK-4-induced calcium mobilization in T cells is enhanced in panic disorder. Akiyoshi, J., Moriyama, T., Isogawa, K., Miyamoto, M., Sasaki, I., Kuga, K., Yamamoto, H., Yamada, K., Fujii, I. J. Neurochem. (1996) [Pubmed]
  16. Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels. Radu, D., Ahlin, A., Svanborg, P., Lindefors, N. Psychopharmacology (Berl.) (2002) [Pubmed]
  17. Effect of the C-terminal tetrapeptide amide of gastrin (CCK-4) and pancreatic polypeptide on gastrointestinal electrical activity in the conscious miniature pig. Wechsung, E., Houvenaghel, A. Peptides (1996) [Pubmed]
  18. The GxxxG-containing transmembrane domain of the CCK4 oncogene does not encode preferential self-interactions. Kobus, F.J., Fleming, K.G. Biochemistry (2005) [Pubmed]
  19. On the biologically active structures of cholecystokinin, little gastrin, and enkephalin in the gastrointestinal system. Pincus, M.R., Carty, R.P., Chen, J., Lubowsky, J., Avitable, M., Shah, D., Scheraga, H.A., Murphy, R.B. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  20. Pentagastrin infusions in patients with panic disorder. I. Symptoms and cardiovascular responses. Abelson, J.L., Nesse, R.M. Biol. Psychiatry (1994) [Pubmed]
  21. Effect of acute tryptophan depletion on behavioral, cardiovascular, and hormonal sensitivity to cholecystokinin-tetrapeptide challenge in healthy volunteers. Koszycki, D., Zacharko, R.M., Le Melledo, J.M., Young, S.N., Bradwejn, J. Biol. Psychiatry (1996) [Pubmed]
  22. Increased ACTH concentrations associated with cholecystokinin tetrapeptide-induced panic attacks in patients with panic disorder. Ströhle, A., Holsboer, F., Rupprecht, R. Neuropsychopharmacology (2000) [Pubmed]
  23. An introduction to neuronal cholecystokinin. Beinfeld, M.C. Peptides (2001) [Pubmed]
  24. Novel regions of chromosomal amplification at 6p21, 5p13, and 12q14 in gastric cancer identified by array comparative genomic hybridization. Gorringe, K.L., Boussioutas, A., Bowtell, D.D. Genes Chromosomes Cancer (2005) [Pubmed]
  25. Investigation of cholecystokinin system genes in panic disorder. Kennedy, J.L., Bradwejn, J., Koszycki, D., King, N., Crowe, R., Vincent, J., Fourie, O. Mol. Psychiatry (1999) [Pubmed]
  26. The role of CCK caerulein, and CCK antagonists in nociception. Baber, N.S., Dourish, C.T., Hill, D.R. Pain (1989) [Pubmed]
  27. Data analysis of kinetic modelling used in drug stability studies: isothermal versus nonisothermal assays. Oliva, A., Llabr??s, M., Fari??a, J.B. Pharm. Res. (2006) [Pubmed]
  28. 10 microg CCK-4 premedication and 35% CO2 challenge in healthy volunteers. Schruers, K., Pols, H., Overbeek, T., Griez, E. Prog. Neuropsychopharmacol. Biol. Psychiatry (2000) [Pubmed]
  29. Effect of CCK-4 on a 35% carbon dioxide challenge in healthy volunteers. Pols, H., Griez, E., Bourin, M., Schruers, K. Prog. Neuropsychopharmacol. Biol. Psychiatry (1999) [Pubmed]
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