Title

The GAP1$\sp{\rm IP4BP}$ protein modulates expression of a calcium-activated potassium channel which facilitates calcium entry

Date of Completion

January 1998

Keywords

Biology, Cell|Health Sciences, Pharmacology|Biology, Animal Physiology|Health Sciences, Oncology

Degree

Ph.D.

Abstract

We have studied the role in store-operated calcium entry of an inositol 1,3,4,5-tetrakisphosphate binding protein (GAP1$\rm\sp{IP4BP}),$ which is a member of GTPase activating protein (GAP1) family. A human erythroleukemia (HEL) cell line was established in which the expression of the GAP1$\rm\sp{IP4BP}$ was significantly reduced using antisense techniques. Reduction of GAP1$\rm\sp{IP4BP}$ expression was associated with an increased calcium entry. Electrophysiological experiments indicated that the expression of intermediate conductance calcium-activated potassium channels was responsible for the enhanced calcium entry. When the calcium-activated potassium channels were blocked by charybdotoxin, store operated calcium entry was similar to that in control cell line. We failed to find any evidence that the GAP1$\rm\sp{IP4BP}$ is directly involved in activation of store-operated calcium entry. Rather our results indicate that the GAP1$\rm\sp{IP4BP}$ regulates the expression of intermediate conductance calcium-activated potassium channels. ^