Activation of Ca2+-activated K+ Channels and Cell Migration by Hepatocyte Growth Factor/Scatter Factor in Madin-Darby Canine Kidney Cells.

Jin, Min

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East Tennessee State University

Activation of Ca2+-activated K+ Channels and Cell Migration by Hepatocyte Growth Factor/Scatter Factor in Madin-Darby Canine Kidney Cells.

dc:creator Jin, Min

thesis:degree_name PhD (Doctor of Philosophy)

dc:date.issued2002

Abstract

dc:description.abstract

Hepatocyte Growth Factor/Scatter Factor (HGF/SF) stimulates migration of various cells and has been linked via Met tyrosine kinase signaling to transformation and the metastatic phenotype. HGF/SF-Met signaling also plays a role in malignancy. Migration of transformed MDCK-F cells depends on activation of a charybdotoxin (ChTX)-sensitive, volume-activated membrane K+ current. Patch-clamp electrophysiology and transwell migration assays were used to study the effects of HGF/SF on membrane K+ currents and cell migration in MDCK II cells. HGF/SF activated membrane K+ currents that increased over 24 hr, and these could be modulated by altering intracellular free calcium concentration [Ca2+]i. HGF/SF also significantly increased MDCK II cell migration. Specific Ca2+-activated K+ channel blockers, ChTX, iberiotoxin (IbTX), stichodactyla toxin (Stk) and clotrimazole (CLT) inhibited HGF/SF stimulation of membrane K+ currents and cell migration. This suggests that the activation of Ca2+-activated K+ channels is necessary for HGF/SF stimulation of MDCK II cell migration. Furthermore, HGF/SF induced ERK phosphorylation, and addition of the MEK inhibitor PD98059 inhibited ERK phosphorylation, as well as HGF/SF stimulation of Ca2+-activated K+ currents and cell migration in MDCK II cells. Taken together, HGF/SF induces phosphorylation of ERK, which plays a role in HGF/SF activation of Ca2+-activated K+ channels and enhancing cell migration in MDCK II cells.

Degree

thesis:*

Name thesis:degree_name: PhD (Doctor of Philosophy)
Level thesis:degree_level: Dissertation - unrestricted
Discipline thesis:degree_discipline: Biomedical Sciences
Year dc:date.issued: 2002

Author and committee

dc:creator, dc:contributor.*

Author dc:creator: Jin, Min

Subjects

dc:subject × 6

Rights

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Statement dc:rights: Copyright by the authors.

Identifiers

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Repository record dc:identifier: https://dc.etsu.edu/etd/712
OAI identifier oai:identifier: oai:dc.etsu.edu:etd-1869

Activation of Ca<sup>2+</sup>-activated K<sup>+</sup> Channels and Cell Migration by Hepatocyte Growth Factor/Scatter Factor in Madin-Darby Canine Kidney Cells.