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Moravcevic K, et al.  (2010) Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids. Cell 143(6):966-77

Abstract: Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to "coincidence detection," allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.CI - Copyright (c) 2010 Elsevier Inc. All rights reserved.

Status: Published Type: Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S. PubMed ID: 21145462

Topics addressed in this paper

Number of different genes curated to this paper: 35

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Topics Genes linked to topics (#1 - 10 )
ARG1 ATG1 ATG7 CAK1 CAM1 CMK1 DFG5 DPS1 ENO2 FDH2
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Mutants/Phenotypes blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Protein Sequence Features blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#11 - 20 )
GAD1 GCN2 GFA1 GIN4 GPA2 GPM3 HSL1 HXK1 KCC4 MPD2
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Disease Gene Related blue ball
Fungal Related Genes/Proteins blue ball blue ball blue ball
Mutants/Phenotypes blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Non-Fungal Related Genes/Proteins blue ball
Primary Literature blue ball blue ball
Protein Physical Properties blue ball
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Topics Genes linked to topics (#21 - 30 )
MUB1 MUM2 PAT1 PEX4 RGD1 SDO1 SDS3 SLM4 SLT2 SPS1
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Topics Genes linked to topics (#31 - 35 )
SPS2 STP22 TAT2 WRS1 YEH2
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