The first 5 amino acids of the carboxyl terminus of phosphatidylinositol transfer protein (PITP) alpha play a critical role in inositol lipid signaling. Transfer activity of PITP is essential but not sufficient for restoration of phospholipase C signaling.

The Journal of Biological Chemistry
S HaraShamshad Cockcroft

Abstract

Phosphatidylinositol transfer protein (PITP) is essential for phospholipase C signaling and for constitutive and regulated vesicular traffic. PITP has a single lipid-binding site that can reversibly bind phosphatidylinositol (PI) and phosphatidylcholine (PC) and transfer these lipids between membrane compartments in vitro. The role of the carboxyl terminus was examined by comparing wild-type PITPalpha with PITPalpha in which 5, 10, and 20 amino acids were deleted from the C terminus. Delta5- and Delta10-PITP had reduced PI and PC transfer activities compared with wild-type PITP, with the effect on PI transfer being more marked than that on PC transfer. Delta20-PITP was inactive at all concentrations tested. All three truncated mutants were unable to restore G-protein-mediated phospholipase Cbeta stimulation in HL-60 cells. Delta5- and Delta10-PITP, but not Delta20-PITP, inhibited the signaling function of wild-type protein without any effect on lipid transfer in vitro. We conclude that (a) the carboxyl terminus of PITP plays a critical role in phospholipase C signaling; (b) the transfer activity is not the only determining factor that dictates the restorative function of PITP in inositol lipid signaling; and (c) the dominant in...Continue Reading

References

Jan 1, 1991·Annual Review of Biochemistry·K W Wirtz
Jan 1, 1990·Sub-cellular Biochemistry·G M Helmkamp
Jun 16, 1995·The Journal of Biological Chemistry·J WestermanK W Wirtz
Aug 4, 1994·Biochimica Et Biophysica Acta·T B GeijtenbeekK W Wirtz

❮ Previous
Next ❯

Citations

Jul 22, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S Cockcroft
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·C Wiedemann, S Cockcroft
Feb 1, 2011·Critical Reviews in Biochemistry and Molecular Biology·Shamshad Cockcroft, Kathryn Garner
Jul 19, 2008·Traffic·Sadaf ShadanShamshad Cockcroft
Dec 3, 2005·The Journal of Biological Chemistry·Yi XieWen-Cheng Xiong
Aug 1, 2013·Physiological Reviews·Tamas Balla
Jan 12, 2001·Molecular Cell Biology Research Communications : MCBRC·G M Thomas, J A Pinxteren
Aug 26, 1998·Biochimica Et Biophysica Acta·M FangV A Bankaitis
May 11, 2007·Biochimica Et Biophysica Acta·Shamshad Cockcroft, Nicolas Carvou

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.