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Are Ligands for the
Integrin 
v1
Departments of
*Medicine and
The multipotential cytokine transforming growth factor-Cell Biology and the
Kaplan Cancer Center and the Raymond and Beverly Sackler
Foundation Laboratory, New York University School of Medicine, New
York, New York 10016; and
§Cellular Biochemistry and
Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York,
New York 10021
(TGF-) is secreted in a latent form. Latency results from the
noncovalent association of TGF- with its processed propeptide dimer,
called the latency-associated peptide (LAP); the complex of the two
proteins is termed the small latent complex. Disulfide bonding between LAP and latent TGF--binding protein (LTBP) produces the most common
form of latent TGF-, the large latent complex. The extracellular matrix (ECM) modulates the activity of TGF-. LTBP and the LAP propeptides of TGF- (isoforms 1 and 3), like many ECM proteins, contain the common integrin-binding sequence RGD. To increase our understanding of latent TGF- function in the ECM, we determined whether latent TGF-1 interacts with integrins. A549 cells
adhered and spread on plastic coated with LAP, small latent
complex, and large latent complex but not on LTBP-coated
plastic. Adhesion was blocked by an RGD peptide, and cells were unable
to attach to a mutant form of recombinant LAP lacking the RGD sequence. Adhesion was also blocked by mAbs to integrin subunits 
v and 1. We purified LAP-binding integrins from extracts of A549
cells using LAP bound to Sepharose. v1 eluted with EDTA. After
purification in the presence of Mn2+, a small amount of
v5 was also detected. A549 cells migrated equally on fibronectin-
and LAP-coated surfaces; migration on LAP was v1 dependent. These
results establish v1 as a LAP-1 receptor. Interactions between
latent TGF- and v1 may localize latent TGF- to the surface
of specific cells and may allow the TGF-1 gene product to initiate
signals by both TGF- receptor and integrin pathways.
Corresponding author. E-mail address:
mungej01{at}popmail.med.nyu.edu.
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