PMID- 10657632
OWN - NLM
STAT- MEDLINE
DCOM- 20000309
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 164
IP  - 4
DP  - 2000 Feb 15
TI  - Membrane cofactor protein (MCP; CD46): isoform-specific tyrosine phosphorylation.
PG  - 1839-46
AB  - Membrane cofactor protein (MCP; CD46) is a widely expressed type 1 transmembrane 
      glycoprotein that inhibits complement activation on host cells. It also is a
      receptor for several pathogens including measles virus, Streptococcus pyogenes,
      Neisseria gonorrhea, and Neisseria meningitidis. That MCP may have signaling
      capability was suggested by its microbial interactions. That is, binding of MCP
      on human monocytes by measles virus hemagglutinin or cross-linking by an anti-MCP
      Ab resulted in IL-12 down-regulation, while binding to MCP by Neisseria on
      epithelial cells produced a calcium flux. Through alternative splicing, MCP is
      expressed on most cells with two distinct cytoplasmic tails of 16 (CYT-1) or 23
      (CYT-2) amino acids. These play pivotal roles in intracellular precursor
      processing and basolateral localization. We investigated the putative signal
      transduction pathway mediated by MCP and demonstrate that CYT-2, but not CYT-1,
      is phosphorylated on tyrosine. We examined MCP tail peptides and performed Ab
      cross-linking experiments on several human cell lines and MCP isoform
      transfectants. We found an MCP peptide of CYT-2 was phosphorylated by a src
      kinase system. Western blots of the cells lines demonstrated that cells bearing
      CYT-2 were also phosphorylated on tyrosine. Additionally, we provide genetic and 
      biochemical evidence that the src family of kinases is responsible for the latter
      phosphorylation events. In particular, the src kinase, Lck, is required for
      phosphorylation of MCP in the Jurkat T cell line. Taken together, these studies
      suggest a src family-dependent pathway for signaling through MCP.
FAU - Wang, G
AU  - Wang G
AD  - Division of Rheumatology, Department of Medicine, Washington University School of
      Medicine, St. Louis, MO 63110, USA.
FAU - Liszewski, M K
AU  - Liszewski MK
FAU - Chan, A C
AU  - Chan AC
FAU - Atkinson, J P
AU  - Atkinson JP
LA  - eng
GR  - R01 AI37618/AI/NIAID 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  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (CD46 protein, human)
RN  - 0 (Complement Inactivator Proteins)
RN  - 0 (Membrane Cofactor Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Isoforms)
RN  - 0 (pervanadate)
RN  - 3WHH0066W5 (Vanadates)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigens, CD/biosynthesis/immunology/*metabolism
MH  - CHO Cells
MH  - Cell Line
MH  - Complement Inactivator Proteins/biosynthesis/immunology/*metabolism
MH  - Cricetinae
MH  - Cytoplasm/metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/physiology
MH  - Membrane Cofactor Protein
MH  - Membrane Glycoproteins/biosynthesis/immunology/*metabolism
MH  - Molecular Sequence Data
MH  - Peptide Fragments/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Isoforms/biosynthesis/immunology/metabolism
MH  - Proto-Oncogene Proteins pp60(c-src)/metabolism
MH  - Substrate Specificity
MH  - Tyrosine/*metabolism
MH  - Vanadates/pharmacology
EDAT- 2000/02/05 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - ji_v164n4p1839 [pii]
AID - 10.4049/jimmunol.164.4.1839 [doi]
PST - ppublish
SO  - J Immunol. 2000 Feb 15;164(4):1839-46. doi: 10.4049/jimmunol.164.4.1839.