PMID- 10604475
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20191210
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 402
IP  - 6762
DP  - 1999 Dec 9
TI  - Binding of paxillin to alpha4 integrins modifies integrin-dependent biological
      responses.
PG  - 676-81
AB  - The alpha4 integrins are indispensable for embryogenesis, haematopoiesis and
      immune responses, possibly because alpha4 regulates cellular functions
      differently from other integrins through its cytoplasmic tail. We used novel
      mimics of the alpha4 tail to identify molecules that could account for
      alpha4-specific signalling. Here we report that the alpha4 tail, but not several 
      other alpha-subunit tails, binds tightly to the signalling adaptor paxillin.
      Paxillin physically associated with alpha4 integrins in Jurkat T cells at high
      stoichiometry, and joining the alpha4 tail to alphaIIb resulted in a complex of
      integrin alphaIIbbeta3 with paxillin. This association markedly enhanced the
      rates of alphaIIbbeta3-dependent phosphorylation of focal adhesion kinase and
      cell migration. It also reduced cell spreading, focal adhesion and stress fibre
      formation. A point mutation within the alpha4 tail that disrupts paxillin binding
      reversed all of these effects. Furthermore, alpha4beta1-dependent adhesion to
      VCAM-1 led to spreading of mouse embryonic fibroblasts derived from paxillin-null
      but not from wild-type mice. Thus, the tight association of paxillin with the
      alpha4 tail leads to distinct biochemical and biological responses to
      integrin-mediated cell adhesion.
FAU - Liu, S
AU  - Liu S
AD  - Department of Vascular Biology, The Scripps Research Institute, La Jolla,
      California 92037, USA.
FAU - Thomas, S M
AU  - Thomas SM
FAU - Woodside, D G
AU  - Woodside DG
FAU - Rose, D M
AU  - Rose DM
FAU - Kiosses, W B
AU  - Kiosses WB
FAU - Pfaff, M
AU  - Pfaff M
FAU - Ginsberg, M H
AU  - Ginsberg MH
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, CD)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LIM Domain Proteins)
RN  - 0 (LPXN protein, human)
RN  - 0 (Lpxn protein, mouse)
RN  - 0 (PXN protein, human)
RN  - 0 (Paxillin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Pxn protein, mouse)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TGFB1I1 protein, human)
RN  - 0 (Tgfb1i1 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 143198-26-9 (Integrin alpha4)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - CHO Cells
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Movement
MH  - Cricetinae
MH  - Cytoskeletal Proteins/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Humans
MH  - Integrin alpha4
MH  - Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - LIM Domain Proteins
MH  - Mice
MH  - Molecular Mimicry
MH  - Paxillin
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Recombinant Fusion Proteins/metabolism
MH  - Transcription Factors
MH  - Tyrosine/metabolism
EDAT- 1999/12/22 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/22 09:00
PHST- 1999/12/22 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/22 09:00 [entrez]
AID - 10.1038/45264 [doi]
PST - ppublish
SO  - Nature. 1999 Dec 9;402(6762):676-81. doi: 10.1038/45264.