Specificity and promiscuity in phosphoinositide binding by pleckstrin homology domains.

@article{Kavran1998SpecificityAP,
  title={Specificity and promiscuity in phosphoinositide binding by pleckstrin homology domains.},
  author={Jennifer M Kavran and Dr. Ernst Klein and Amy Lee and Marco Falasca and Steven Jay Isakoff and Edward Y Skolnik and Mark A Lemmon},
  journal={The Journal of biological chemistry},
  year={1998},
  volume={273 46},
  pages={30497-508}
}
Pleckstrin homology (PH) domains are small protein modules involved in recruitment of signaling molecules to cellular membranes, in some cases by binding specific phosphoinositides. We describe use of a convenient "dot-blot" approach to screen 10 different PH domains for those that recognize particular phosphoinositides. Each PH domain bound phosphoinositides in the assay, but only two (from phospholipase C-delta1 and Grp1) showed clear specificity for a single species. Using soluble inositol… CONTINUE READING
Highly Influential
This paper has highly influenced a number of papers. REVIEW HIGHLY INFLUENTIAL CITATIONS

Connections & Topics

Mentioned Connections BETA
Using soluble inositol phosphates , we show that the Grp1 PH domain ( originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ) binding ) binds specifically to D - myo - inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P4 ) ( the PtdIns(3,4,5)P3 headgroup ) with KD = 27.3 nM , but binds D - myo - inositol 1,3,4-trisphosphate ( Ins(1,3,4)P3 ) or D - myo - inositol 1,4,5-trisphosphate ( Ins(1,4,5)P3 ) over 80-fold more weakly .
Using soluble inositol phosphates , we show that the Grp1 PH domain ( originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ) binding ) binds specifically to D - myo - inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P4 ) ( the PtdIns(3,4,5)P3 headgroup ) with KD = 27.3 nM , but binds D - myo - inositol 1,3,4-trisphosphate ( Ins(1,3,4)P3 ) or D - myo - inositol 1,4,5-trisphosphate ( Ins(1,4,5)P3 ) over 80-fold more weakly .
Using soluble inositol phosphates , we show that the Grp1 PH domain ( originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ) binding ) binds specifically to D - myo - inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P4 ) ( the PtdIns(3,4,5)P3 headgroup ) with KD = 27.3 nM , but binds D - myo - inositol 1,3,4-trisphosphate ( Ins(1,3,4)P3 ) or D - myo - inositol 1,4,5-trisphosphate ( Ins(1,4,5)P3 ) over 80-fold more weakly .
Using soluble inositol phosphates , we show that the Grp1 PH domain ( originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ) binding ) binds specifically to D - myo - inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P4 ) ( the PtdIns(3,4,5)P3 headgroup ) with KD = 27.3 nM , but binds D - myo - inositol 1,3,4-trisphosphate ( Ins(1,3,4)P3 ) or D - myo - inositol 1,4,5-trisphosphate ( Ins(1,4,5)P3 ) over 80-fold more weakly .
Using soluble inositol phosphates , we show that the Grp1 PH domain ( originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ) binding ) binds specifically to D - myo - inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P4 ) ( the PtdIns(3,4,5)P3 headgroup ) with KD = 27.3 nM , but binds D - myo - inositol 1,3,4-trisphosphate ( Ins(1,3,4)P3 ) or D - myo - inositol 1,4,5-trisphosphate ( Ins(1,4,5)P3 ) over 80-fold more weakly .
Using soluble inositol phosphates , we show that the Grp1 PH domain ( originally cloned on the basis of its phosphatidylinositol 3,4,5-trisphosphate ( PtdIns(3,4,5)P3 ) binding ) binds specifically to D - myo - inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P4 ) ( the PtdIns(3,4,5)P3 headgroup ) with KD = 27.3 nM , but binds D - myo - inositol 1,3,4-trisphosphate ( Ins(1,3,4)P3 ) or D - myo - inositol 1,4,5-trisphosphate ( Ins(1,4,5)P3 ) over 80-fold more weakly .
Together with data presented in the literature , our results suggest that many PH domains bind similarly to multiple phosphoinositides ( and in some cases phosphatidylserine ) , and are likely to be regulated in vivo by the most abundant species to which they bind .
Together with data presented in the literature , our results suggest that many PH domains bind similarly to multiple phosphoinositides ( and in some cases phosphatidylserine ) , and are likely to be regulated in vivo by the most abundant species to which they bind .
All Topics