PMID- 8643625
OWN - NLM
STAT- MEDLINE
DCOM- 19960717
LR  - 20191210
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 93
IP  - 11
DP  - 1996 May 28
TI  - Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.
PG  - 5615-8
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder with the 
      most severe pathology in the T lymphocytes and platelets. The disease arises from 
      mutations in the gene encoding the WAS protein. T lymphocytes of affected males 
      with WAS exhibit a severe disturbance of the actin cytoskeleton, suggesting that 
      the WAS protein could regulate its organization. We show here that WAS protein 
      interacts with a member of the Rho family of GTPases, Cdc42. This interaction, 
      which is guanosine 5'-triphosphate (GTP)-dependent, was detected in cell lysates, 
      in transient transfections and with purified recombinant proteins. A weaker 
      interaction was also detected with Rac1 using WAS protein from cell lysates. It 
      was also found that different mutant WAS proteins from three affected males 
      retained their ability to interact with Cdc42 and that the level of expression of 
      the WAS protein in these mutants was only 2-5% of normal. Taken together these 
      data suggest that the WAS protein might function as a signal transduction adaptor 
      downstream of Cdc42, and in affected males, the cytoskeletal abnormalities may 
      result from a defect in Cdc42 signaling.
FAU - Kolluri, R
AU  - Kolluri R
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
FAU - Tolias, K F
AU  - Tolias KF
FAU - Carpenter, C L
AU  - Carpenter CL
FAU - Rosen, F S
AU  - Rosen FS
FAU - Kirchhausen, T
AU  - Kirchhausen T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Peptides)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (WAS protein, human)
RN  - 0 (Wiskott-Aldrich Syndrome Protein)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein, Saccharomyces cerevisiae)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cell Cycle Proteins/chemistry/*metabolism
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - GTP Phosphohydrolases/*metabolism
MH  - GTP-Binding Proteins/chemistry/*metabolism
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Peptides/chemical synthesis/immunology
MH  - Proteins/chemistry/genetics/*metabolism
MH  - Recombinant Fusion Proteins/biosynthesis/chemistry/metabolism
MH  - Reference Values
MH  - T-Lymphocytes/*metabolism
MH  - Transfection
MH  - Wiskott-Aldrich Syndrome/blood/genetics/*physiopathology
MH  - Wiskott-Aldrich Syndrome Protein
MH  - cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
PMC - PMC39296
EDAT- 1996/05/28 00:00
MHDA- 1996/05/28 00:01
PMCR- 1996/11/28
CRDT- 1996/05/28 00:00
PHST- 1996/05/28 00:00 [pubmed]
PHST- 1996/05/28 00:01 [medline]
PHST- 1996/05/28 00:00 [entrez]
PHST- 1996/11/28 00:00 [pmc-release]
AID - 10.1073/pnas.93.11.5615 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1996 May 28;93(11):5615-8. doi: 
      10.1073/pnas.93.11.5615.