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Gene Review

Frk  -  fyn-related kinase

Mus musculus

Synonyms: BSK, BSK/IYK, Beta-cell Src-homology tyrosine kinase, Bsk, C85044, ...
 
 
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Disease relevance of Frk

  • Cytokine-induced islet toxicity was reduced in islets isolated from FRK/RAK knockout mice and this occurred without effects on the production of nitric oxide [1].
  • A Borrelia garinii strain named Rio1 was isolated from both a direct BSK medium culture and a mouse ear-punch biopsy culture [2].
  • To determine by xenodiagnosis length and concentrations of spirochetemias produced by Borrelia burgdorferi in white-footed mice (Peromyscus leucopus), laboratory reared mice were inoculated with either spirochete-containing tick suspensions or BSK II spirochete culture and were exposed for as long as three months to larval Ixodes dammini [3].
 

High impact information on Frk

  • Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak [4].
  • Ultrastructural analysis of intestinal enterocytes did not identify defects in brush border morphology or structural polarization, demonstrating that Frk/rak is dispensable for intestinal cytodifferentiation [4].
  • Treatment of the cells with the MEK inhibitor PD98059 did not reduce the GTK-dependent increased in neurite outgrowth [5].
  • We report that PC12 cells stably overexpressing GTK exhibit a larger fraction of cells with neurites as compared with control cells, and this response is not accompanied by an increased ERK activity [5].
  • We have designated the gene as BSK (beta-cell Src-homology tyrosine kinase) [6].
 

Biological context of Frk

  • Cloning of BSK, a murine FRK homologue with a specific pattern of tissue distribution [6].
  • This effect was dependent on intracellular signal transduction pathways activated or enhanced by GTK and SHB overexpression, since the proliferation of acinar cells, located in the vicinity of the islets, was equal in the transgenic and control mice [7].
  • Addition of the nitric oxide inhibitor nitroarginine to FRK/RAK knockout islets exposed to cytokines decreased cell death to a basal level [1].
  • No evidence for in vitro phosphorylation of the C-terminal regulatory sites Tyr-497 and Tyr-504 was obtained, nor was there any indication of in vitro regulation of FRK/RAK kinase activity [1].
  • In normal islets, cytokine-induced cell death was inhibited by the addition of two FRK/RAK inhibitors, SU4984 and D-65495, or by transfection with short interfering RNA against FRK/RAK [1].
 

Anatomical context of Frk

 

Associations of Frk with chemical compounds

  • GTK- and SHB-transgenic mice, treated with a sub-diabetogenic dose of the beta-cell toxin streptozotocin (STZ) on day 0 and subjected to a glucose tolerance test on day 3, exhibited an impaired glucose tolerance in comparison with the STZ-treated control mice [7].
 

Analytical, diagnostic and therapeutic context of Frk

  • Northern blots using poly(A)+RNA from non-beta-cell tissues showed that the BSK cDNA hybridized to three mRNA transcripts (2.9, 3.1 and 5.0 kb) present in kidney, liver and lung [6].
  • To further investigate the importance of GTK and SHB for beta-cell death and proliferation, these mice were subjected to a 60% partial pancreatectomy (Px) or a sham-operation and beta-cell replication was determined by autoradiographic detection of [(3)H]thymidine incorporation into islet cells positively stained for insulin [7].
  • Infection status of hosts was assessed 4 wk later by culture of ear-punch biopsies in BSK II medium and by indirect immunofluorescence [8].

References

  1. The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell cytotoxicity. Welsh, M., Welsh, C., Ekman, M., Dixelius, J., Hägerkvist, R., Annerén, C., Akerblom, B., Mahboobi, S., Chandrasekharan, S., Liu, E.T. Biochem. J. (2004) [Pubmed]
  2. Use of the C3H/He Lyme disease mouse model for the recovery of a Spanish isolate of Borrelia garinii from erythema migrans lesions. Oteo, J.A., Backenson, P.B., del Mar Vitutia, M., García Moncó, J.C., Rodríguez, I., Escudero, R., Anda, P. Res. Microbiol. (1998) [Pubmed]
  3. Lyme borreliosis: a relapsing fever-like disease? Burgdorfer, W., Schwan, T.G. Scandinavian journal of infectious diseases. Supplementum. (1991) [Pubmed]
  4. Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak. Chandrasekharan, S., Qiu, T.H., Alkharouf, N., Brantley, K., Mitchell, J.B., Liu, E.T. Mol. Cell. Biol. (2002) [Pubmed]
  5. GTK, a Src-related tyrosine kinase, induces nerve growth factor-independent neurite outgrowth in PC12 cells through activation of the Rap1 pathway. Relationship to Shb tyrosine phosphorylation and elevated levels of focal adhesion kinase. Annerén, C., Reedquist, K.A., Bos, J.L., Welsh, M. J. Biol. Chem. (2000) [Pubmed]
  6. Cloning of BSK, a murine FRK homologue with a specific pattern of tissue distribution. Oberg-Welsh, C., Welsh, M. Gene (1995) [Pubmed]
  7. Dual role of the tyrosine kinase GTK and the adaptor protein SHB in beta-cell growth: enhanced beta-cell replication after 60% pancreatectomy and increased sensitivity to streptozotocin. Annerén, C. J. Endocrinol. (2002) [Pubmed]
  8. Transmission of Borrelia burgdorferi by Ixodes pacificus nymphs and reservoir competence of deer mice (Peromyscus maniculatus) infected by tick-bite. Peavey, C.A., Lane, R.S. J. Parasitol. (1995) [Pubmed]
 
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