Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities - PubMed (original) (raw)

Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities

S Dowler et al. Biochem J. 2000.

Abstract

The second messenger phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] is generated by the action of phosphoinositide 3-kinase (PI 3-kinase), and regulates a plethora of cellular processes. An approach for dissecting the mechanisms by which these processes are regulated is to identify proteins that interact specifically with PtdIns(3,4,5)P(3). The pleckstrin homology (PH) domain has become recognized as the specialized module used by many proteins to interact with PtdIns(3,4,5)P(3). Recent work has led to the identification of a putative phosphatidylinositol 3,4,5-trisphosphate-binding motif (PPBM) at the N-terminal regions of PH domains that interact with this lipid. We have searched expressed sequence tag databases for novel proteins containing PH domains possessing a PPBM. Surprisingly, many of the PH domains that we identified do not bind PtdIns(3,4,5)P(3), but instead possess unexpected and novel phosphoinositide-binding specificities in vitro. These include proteins possessing PH domains that interact specifically with PtdIns(3,4)P(2) [TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns4P [FAPP1 (phosphatidylinositol-four-phosphate adaptor protein-1)], PtdIns3P [PEPP1 (phosphatidylinositol-three-phosphate-binding PH-domain protein-1) and AtPH1] and PtdIns(3,5)P(2) (centaurin-beta2). We have also identified two related homologues of PEPP1, termed PEPP2 and PEPP3, that may also interact with PtdIns3P. This study lays the foundation for future work to establish the phospholipid-binding specificities of these proteins in vivo, and their physiological role(s).

PubMed Disclaimer

Similar articles

Cited by

References

    1. Curr Opin Cell Biol. 1999 Apr;11(2):219-25 - PubMed
    1. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4633-8 - PubMed
    1. Biochem J. 1999 Jun 1;340 ( Pt 2):359-63 - PubMed
    1. FEBS Lett. 1999 May 28;451(3):220-6 - PubMed
    1. Cell. 1999 Jun 25;97(7):817-20 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources