PMID- 11984006
OWN - NLM
STAT- MEDLINE
DCOM- 20020614
LR  - 20211203
IS  - 1076-1551 (Print)
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Linking)
VI  - 8
IP  - 1
DP  - 2002 Jan
TI  - The Chediak-Higashi protein interacts with SNARE complex and signal transduction 
      proteins.
PG  - 56-64
AB  - BACKGROUND: Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency 
      disease characterized by giant lysosomes and impaired leukocyte degranulation. 
      CHS results from mutations in the lysosomal trafficking regulator (LYST) gene, 
      which encodes a 425-kD cytoplasmic protein of unknown function. The goal of this 
      study was to identify proteins that interact with LYST as a first step in 
      understanding how LYST modulates lysosomal exocytosis. MATERIALS AND METHODS: 
      Fourteen cDNA fragments, covering the entire coding domain of LYST, were used as 
      baits to screen five human cDNA libraries by a yeast two-hybrid method, modified 
      to allow screening in the activation and the binding domain, three selectable 
      markers, and more stringent confirmation procedures. Five of the interactions 
      were confirmed by an in vitro binding assay. RESULTS: Twenty-one proteins that 
      interact with LYST were identified in yeast two-hybrid screens. Four 
      interactions, confirmed directly, were with proteins important in vesicular 
      transport and signal transduction (the SNARE-complex protein HRS, 14-3-3, and 
      casein kinase II). CONCLUSIONS: On the basis of protein interactions, LYST 
      appears to function as an adapter protein that may juxtapose proteins that 
      mediate intracellular membrane fusion reactions. The pathologic manifestations 
      observed in CHS patients and in mice with the homologous mutation beige suggest 
      that understanding the role of LYST may be relevant to the treatment of not only 
      CHS but also of diseases such as asthma, urticaria, and lupus, as well as to the 
      molecular dissection of the CHS-associated cancer predisposition.
FAU - Tchernev, Velizar T
AU  - Tchernev VT
AD  - CuraGen Corporation, New Haven, CT 06511, USA. velizart@molecularstaging.com
FAU - Mansfield, Traci A
AU  - Mansfield TA
FAU - Giot, Loic
AU  - Giot L
FAU - Kumar, A Madan
AU  - Kumar AM
FAU - Nandabalan, Krishnan
AU  - Nandabalan K
FAU - Li, Ying
AU  - Li Y
FAU - Mishra, Vishnu S
AU  - Mishra VS
FAU - Detter, John C
AU  - Detter JC
FAU - Rothberg, Jonathan M
AU  - Rothberg JM
FAU - Wallace, Margaret R
AU  - Wallace MR
FAU - Southwick, Frederick S
AU  - Southwick FS
FAU - Kingsmore, Stephen F
AU  - Kingsmore SF
LA  - eng
GR  - P01 AI039824/AI/NIAID NIH HHS/United States
GR  - U19 HD077693/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (14-3-3 Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LYST protein, human)
RN  - 0 (Lyst protein, mouse)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Peptide Fragments)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Troponin I)
RN  - 0 (Vesicular Transport Proteins)
RN  - 0 (hepatocyte growth factor-regulated tyrosine kinase substrate)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - 14-3-3 Proteins
MH  - Animals
MH  - Casein Kinase II
MH  - DNA, Complementary/genetics
MH  - Endosomal Sorting Complexes Required for Transport
MH  - Exocytosis/physiology
MH  - Gene Library
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lysosomes/metabolism
MH  - Macromolecular Substances
MH  - Mice
MH  - Peptide Fragments/metabolism
MH  - Phosphoproteins/*metabolism
MH  - Protein Interaction Mapping
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proteins/*metabolism
MH  - Recombinant Fusion Proteins/*metabolism
MH  - Signal Transduction/physiology
MH  - Troponin I/*metabolism
MH  - Two-Hybrid System Techniques
MH  - Tyrosine 3-Monooxygenase/*metabolism
MH  - Vesicular Transport Proteins
PMC - PMC2039936
EDAT- 2002/05/02 10:00
MHDA- 2002/06/18 10:01
PMCR- 2002/01/01
CRDT- 2002/05/02 10:00
PHST- 2002/05/02 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/05/02 10:00 [entrez]
PHST- 2002/01/01 00:00 [pmc-release]
AID - S1528365802100565 [pii]
PST - ppublish
SO  - Mol Med. 2002 Jan;8(1):56-64.