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The Tyrosine Kinase...
The Tyrosine Kinase GTK : Signal Transduction and Biological Function
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- Annerén, Cecilia (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- ISBN 9155450822
- Uppsala : Acta Universitatis Upsaliensis, 2001
- Engelska 56 s.
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Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1062
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Abstract
Ämnesord
Stäng
- Protein tyrosine kinases play an important role in the regulation of various cellular processes such asgrowth, differentiation and survival. GTK, a novel SRC-like cytoplasmic tyrosine kinase, was recently cloned from a mouse insulinoma cell line and the present work was conducted in order to find a biological function of GTK in insulin producing and neuronal cells. It was observed that kinase active GTK-mutants, expressed in RINm5F cells, transferred to the cell nucleus and increased the levels of the cell cycle regulatory protein p27KIP1, reduced cell growth and stimulated glucagon mRNA expression. Furthermore, wild type GTK induces neurite outgrowth in the rat adrenal pheochromocytoma PC12 cell line, through activation of the RAP1-pathway, suggesting a role of GTK for cell differentiation. Studies using transgenic mice, expressing GTK under the control of the rat insulin 1 promoter, demonstrated a dual role of GTK for β-cell growth: Whereas GTK increases the β-cell mass and causes enhanced β-cell proliferation in response to partial pancreatectomy it also induced β-cell death in response to proinflammatory cytokines and impaired the glucose tolerance in mice treated with the β-cell toxin streptozotocin suggesting a possible role of GTK for β-cell destruction in Type 1 diabetes. We have also observed that GTK-transgenic islets and GTK-expressing RINm5F cells exhibit a reduced insulininduced activation of the insulin receptor substrate (IRS-1 and IRS-2)-pathways, partly due to an increased basal activity of these. GTK was found to associate with and phosphorylate the SH2 domain adapter protein SHB, which could explain many of the GTK-dependent effects both in vitro and in vivo. In summary, the present work suggests that the novel tyrosine kinase GTK is involved in various signal transduction pathways, regulating different cellular responses, such as proliferation, differentiation and survival.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Cell biology
- Protein tyrosine kinases
- GTK
- SHB
- proliferation
- survival
- differentiation
- β cells
- pancreatectomy
- cytokines
- diabetes
- PC12 cells
- NGF
- streptozotocin
- focal adhesion kinase
- RAP1
- Cellbiologi
- Cell biology
- Cellbiologi
- medicinsk cellbiologi
- Medical Cell Biology
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