PMID- 10194441
OWN - NLM
STAT- MEDLINE
DCOM- 19990503
LR  - 20071115
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 8
DP  - 1999 Apr 15
TI  - Human platelets contain SNARE proteins and a Sec1p homologue that interacts with 
      syntaxin 4 and is phosphorylated after thrombin activation: implications for
      platelet secretion.
PG  - 2617-26
AB  - In response to thrombin and other extracellular activators, platelets secrete
      molecules from large intracellular vesicles (granules) to initiate thrombosis.
      Little is known about the molecular machinery responsible for vesicle docking and
      secretion in platelets and the linkage of that machinery to cell activation. We
      found that platelet membranes contain a full complement of interacting
      proteins-VAMP, SNAP-25, and syntaxin 4-that are necessary for vesicle docking and
      fusion with the plasma membrane. Platelets also contain an uncharacterized
      homologue of the Sec1p family that appears to regulate vesicle docking through
      its binding with a cognate syntaxin. This platelet Sec1 protein (PSP) bound to
      syntaxin 4 and thereby excluded the binding of SNAP-25 with syntaxin 4, an
      interaction critical to vesicle docking. As predicted by its sequence, PSP was
      detected predominantly in the platelet cytosol and was phosphorylated in vitro by
      protein kinase C (PKC), a secretion-linked kinase, incorporating 0.87 +/- 0.11
      mol of PO4 per mole of protein. PSP was also specifically phosphorylated in
      permeabilized platelets after cellular stimulation by phorbol esters or thrombin 
      and this phosphorylation was blocked by the PKC inhibitor Ro-31-8220.
      Phosphorylation by PKC in vitro inhibited PSP from binding to syntaxin 4. Taken
      together, these studies indicate that platelets, like neurons and other cells
      capable of regulated secretion, contain a unique complement of interacting
      vesicle docking proteins and PSP, a putative regulator of vesicle docking. The
      PKC-dependent phosphorylation of PSP in activated platelets and its inhibitory
      effects on syntaxin 4 binding provide a novel functional link that may be
      important in coupling the processes of cell activation, intracellular signaling, 
      and secretion.
FAU - Reed, G L
AU  - Reed GL
AD  - Cardiovascular Biology Laboratory, Harvard School of Public Health, Cardiac Unit,
      Massachusetts General Hospital, Boston, MA, USA. reed@cvlab.harvard.edu
FAU - Houng, A K
AU  - Houng AK
FAU - Fitzgerald, M L
AU  - Fitzgerald ML
LA  - eng
SI  - GENBANK/AF032922
GR  - R01 HL57314-01/HL/NHLBI 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  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Membrane Proteins)
RN  - 0 (Munc18 Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Qa-SNARE Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SNAP25 protein, human)
RN  - 0 (SNARE Proteins)
RN  - 0 (Synaptosomal-Associated Protein 25)
RN  - 0 (Vesicular Transport Proteins)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.21.5 (Thrombin)
SB  - AIM
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Blood Platelets/drug effects/*physiology
MH  - Cell Fusion/physiology
MH  - Cell Membrane/physiology
MH  - Cloning, Molecular
MH  - Cytosol/metabolism
MH  - Humans
MH  - Membrane Proteins/*blood/genetics
MH  - Molecular Sequence Data
MH  - Munc18 Proteins
MH  - Nerve Tissue Proteins/*blood
MH  - Phosphorylation
MH  - Platelet Activation
MH  - Polymerase Chain Reaction
MH  - Protein Kinase C/blood
MH  - Qa-SNARE Proteins
MH  - Recombinant Proteins/biosynthesis
MH  - SNARE Proteins
MH  - Synaptosomal-Associated Protein 25
MH  - Thrombin/pharmacology/*physiology
MH  - *Vesicular Transport Proteins
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Apr 15;93(8):2617-26.