COMMUNICATION
Integrin-associated Protein Is a Ligand for the P84 Neural
Adhesion Molecule*
Peihua
Jiang
,
Carl F.
Lagenaur
, and
Vinodh
Narayanan
§¶
From the
Department of Neurobiology and the
§ Department of Pediatrics, University of Pittsburgh School
of Medicine and ¶ The Children's Hospital of Pittsburgh,
Pittsburgh, Pennsylvania 15213
 |
ABSTRACT |
P84 (also known as SHPS-1, BIT, and SIRP) is a
heterophilic adhesive membrane protein involved in receptor tyrosine
kinase signaling that is found at synapses in the mammalian central
nervous system and in non-neural tissues. We have identified a binding partner for P84 using an expression cloning strategy. Here we report
that integrin-associated protein (IAP/CD47) is a predominant binding
partner of P84. Immunohistochemistry reveals a virtually identical
distribution of P84 and IAP in a variety of adult brain regions.
Because IAP has been implicated in cell signaling in cells of the
immune system, P84 and IAP represent a heterophilic binding pair that
is likely to be involved in bi-directional signaling at the synapse and
in other tissues.
 |
INTRODUCTION |
A number of adhesive molecules have been shown to be important for
formation and maintenance of synaptic connections in the CNS.1 Immunoglobulins,
cadherins, integrins, as well as proteoglycans and their receptors
appear to contribute to synapse formation (1-4). We originally
identified the immunoglobulin family member P84 by virtue of its
adhesive properties when tested with cerebellar and neocortical neurons
(5). The ability of P84 to promote neurite outgrowth and stimulate
robust filopodial extension in growth cones suggested that its ligand
was also capable of signal transduction (5, 6). The association of P84
with synaptic regions in the CNS suggested that it might be another
candidate molecule for mediation of synaptic adhesion. We recently
cloned the P84 gene and discovered that it was identical to SHPS-1,
BIT, and SIRP-
molecules that had been identified by their binding to the cytoplasmic tyrosine phosphatase, SHP-2 (7-10). P84 contains a
single transmembrane domain, three extracellular Ig-like domains, and a
cytoplasmic segment that includes tyrosine phosphorylation sites. These
phosphotyrosines correspond to sites recognized by SH2-containing
segments of the SHP-2 phosphatase. There remain many intriguing
questions regarding P84 that are to be answered, including how and why
this molecule is localized at the synapse, what the downstream effects
of P84 activation are, and what extracellular molecules are involved in
initiating signaling via P84.
To address this last question, we undertook an expression-cloning
approach to identify ligands that bound to the extracellular segment of
P84. We have discovered that a predominant ligand for P84 is the
integrin-associated protein (IAP/CD47). In addition to its expression
in lymphocytes and other extraneural tissues, IAP was known to be
expressed in the brain, and its expression has recently been associated
with memory formation (11). Antibodies against IAP blocked the adhesion
of cerebellar neurons, erythrocytes, and thymocytes to P84-coated
substrates. We also showed that the distribution of P84 and IAP in the
cerebellum and retina were very similar and consistent with their
participation in a heterophilic synaptic adhesion complex.
 |
EXPERIMENTAL PROCEDURES |
Production of Alkaline Phosphatase Fusion Proteins--
Alkaline
phosphatase (AP)-tag2 and AP-tag4 plasmids were a generous gift of J. Flanagan (Harvard University, School of Medicine). The sequences
corresponding to the signal peptide and extracellular segment of murine
P84 were amplified by polymerase chain reaction, and cloned into the
BglII site of the AP-tag 2 vector. This plasmid was
transfected with LipofectAMINE (Life Technologies Inc.) into 293TWT cells (Edge Biosystems), and the supernatant was
collected between days 4 and 8. The supernatant was monitored for
phosphatase activity using a synthetic substrate,
p-nitrophenyl phosphate (Sigma 104 phosphatase substrate)
(12). The fusion protein was affinity purified and analyzed by
SDS-polyacrylamide gel electrophoresis. As a control, 293T cells were
transfected with the AP-tag4 plasmid, which directed the secretion of
AP alone. For P84 ligand staining in situ, the P84-AP fusion
protein (culture supernatant) was incubated with tissue sections or
cells (receptor alkaline phosphatase (RAP) in situ)
following the method of Cheng and Flanagan (13). The extracellular
domain of IAP was cloned into the AP-tag2 vector, and an IAP-AP fusion
protein was produced as described above for P84-AP. Immunopurified P84,
L1, and neural cell adhesion molecule (N-CAM) were spotted on
nitrocellulose, blocked, and incubated with IAP-AP for 30 min. After
washing, AP activity was detected with NBT/BCIP.
Expression Cloning--
An adult mouse brain cDNA library
was obtained from Edge Biosystems Inc. (Gaithersburg, MD). This library
was constructed in the pEAK8 plasmid vector. Forty pools of about 2500 colonies each were plated. These were harvested into liquid medium, and an aliquot of each was saved. DNA was extracted from the remainder of
each sample (Perfect Prep Kit, 5 Prime-3 Prime, Inc.). DNA from each
pool (0.3-0.5 µg) was transiently transfected into COS-7 cells in
6-well plates using LipofectAMINE. After 48 h, cells were
incubated with P84-AP fusion protein and stained. From a single
positive pool, a single cDNA clone was purified by sib selection.
Briefly, the culture corresponding to the positive pool was replica
plated onto nylon membranes, and one of these membranes divided into
ten segments. DNA was extracted from each of the subpools and tested
for staining with the P84-AP fusion protein. This process was iterated
until a single positive cDNA clone was obtained. As a control,
transfected and untransfected cells were stained with P84-AP and AP
alone. The positive clones were sequenced using vector-specific primers
(pEAK8.for -ggatcttggttcattctcaa; and pEAK8.rev -ctggatgcaggctactctag)
and with gene-specific primers.
Immunostaining of Cells and Tissue--
Animals were perfused
with 4% paraformaldehyde in PBS, and dissected tissues were
cryoprotected in 30% sucrose. Cryostat sections were collected on
pretreated slides. The monoclonal P84 and IAP (miap301, PharMingen)
antibodies were previously described (5, 14). Sections were stained
with primary antibodies for 1 h and incubated with FITC-conjugated
goat anti-rat secondary antibody (Cappel) for 30 min. The staining was
examined with fluorescence microscopy.
Cell Adhesion Assays--
Coverslips were first coated with
nitrocellulose (Schleicher and Schuell, Inc.) as described previously
(6). Purified proteins (P84, P84-AP, laminin, or miap301 antibody) were
spotted at the center of the coated coverslips in 5-mm spots. The
substrate solution was aspirated after 5 min. Coverslips were blocked
with 1% BSA in PBS followed by medium containing 10% horse serum.
Laminin was a generous gift of Dr. J. Hassel (University of
Pittsburgh). Cerebellar cells were prepared as described previously
(15). Blood was collected from adult mice in heparinized tubes, washed twice, and suspended in 1% BSA containing PBS at a titer of 5 × 106 cell/ml. Thymus was removed from young mice, washed
several times with PBS, and cut into several small pieces to release
free thymocytes. After several washes, thymocytes were resuspended in
PBS containing 1% BSA at a titer of 5 × 106 cell/ml.
Purified miap301 (0.5 mg/ml) was added to suspended cells at 1:100
ratio and then allowed to bind for 20 min at 0 °C. After plating on
P84-coated coverslips and incubation for 2 h, cells were washed
three times with PBS, fixed with 4% paraformaldehyde for 10 min, and counted.
 |
RESULTS |
Production of a Soluble P84 Ectodomain Fusion Protein--
To
facilitate the cloning of P84-binding proteins, a cDNA encoding the
P84 ectodomain was inserted into the AP-tag2 vector (13). This plasmid
directs expression of a soluble fusion protein with human alkaline
phosphatase at the carboxyl-terminal end (Fig. 1A). 293T cells transiently
transfected with this construct secreted the recombinant P84-AP, and
this fusion protein was purified with an anti-P84 affinity column (Fig.
1B). Because native P84 was known to be a good substrate for
cerebellar cell attachment and neurite outgrowth, we tested the
purified P84-AP fusion protein in a cell adhesion assay. The purified
P84-AP was immobilized on Petri dishes, and mouse cerebellar cells were
allowed to attach and grow for 24 h. There was no obvious
difference in the attachment of neurons or pattern of neurite growth on
native P84 or P84-AP (Fig. 1C, and see Ref. 5). RAP in
situ staining (13) was done to examine P84 binding activity in the
brain regions which were known to contain P84. In the cerebellum, the
molecular layer was heavily stained, and a pattern consistent with
synaptic glomeruli in the granule cell layer was observed (Fig.
1D). This P84-AP cerebellar staining was very similar to
that seen with P84 antibody staining (7), which suggested that the
P84-AP probe detected an endogenous extracellular binding partner for
P84. No staining was observed with AP alone (Fig. 1E).

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Fig. 1.
P84 ectodomain fusion protein.
A, diagram of the P84 ectodomain fused to human alkaline
phosphatase. B, SDS-polyacrylamide gel electrophoresis of
purified P84-AP (lane 2); Sigma high molecular weight
markers (lane 1). The major band in lane 2 lies
between the 116 and 205 kDa markers. C, postnatal mouse
cerebellar neurons attach to P84-AP and extend neurites after 24 h
in vitro. D and E, RAP in
situ staining of sections of adult mouse cerebellum, stained with
P84-AP (panel D) and with AP alone (panel E).
M indicates molecular layer, and G indicates
granule cell layer. Bar in panels C
and E indicate 0.1 mm.
|
|
Expression Cloning of a P84-binding Protein--
To search for
P84-binding proteins, we screened a mouse brain cDNA library with
the P84-AP fusion protein. Transfected cells were screened for P84-AP
binding using the procedure described by Cheng and Flanagan (13). AP
without the P84 ectodomain was included as a negative control. From the
40 pools screened (about 2,500 colonies in each pool), two positive
pools were identified. From one of these, a single positive cDNA
clone was purified (Fig. 2). Sequencing
of the cDNA derived from this clone revealed that it was the
brain-specific form of mouse IAP (form 4) (16). This form of IAP has
the longest cytoplasmic domain of all the forms of IAP. We also noticed
that a region of 63 nucleotides that encode 21 amino acids in the
extracellular domain near the first transmembrane region (but not in
IgV-like domain) is lacking in this particular clone. This 21 amino
acid region is also lacking in some mouse, rat, and human IAP forms
(Fig. 3A) (17). An IAP-AP
fusion protein was tested for binding on purified P84, L1, and N-CAM.
Binding was observed on P84 but not on the other molecules (Fig.
3B).

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Fig. 2.
P84-AP staining of transfected COS-7
cells. Panels A through C show successive
stages of enrichment by sib selection of a single positive clone from
an adult mouse brain cDNA library. Panel D
shows lack of staining by AP alone of cells transfected with the same
cDNA used in panel C. Bar in panel
B indicates 50 µM, and bar in panel
D indicates 30 µM.
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Fig. 3.
Comparison of P84 ligand to IAP.
A, diagram showing the structure of mouse IAP and the P84
ligand. B, IAP-AP fusion protein binds directly to purified
brain P84 but not L1 or N-CAM. No binding is seen with AP alone.
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|
Anti-IAP Antibody Can Block Cell Binding to P84--
Freshly
dissociated cerebellar cells can bind to native P84 within 10 min. We
tested whether IAP was present on trypsin-dissociated cerebellar cells.
Anti-IAP (miap301) was bound to nitrocellulose-coated coverslips, and
cerebellar cells were tested for their ability to bind to these
coverslips. Cell binding to this antibody occurred within 10 min; with
overnight incubation, the cells remained attached to the antibody
substrate and extended neurites (data not shown). To determine whether
IAP represented a major binding partner for P84, we attempted to block
neuronal IAP with the miap301 antibody which is directed against the
IgV domain of IAP. We then tested antibody-treated neurons for their
ability to bind to purified brain P84. Freshly dissociated cerebellar
cells were incubated with anti-IAP antibody or in antibody-free media
for 30 min at 0 °C and then plated on P84-coated coverslips. Cells
were allowed to attach for 2 h at 37 °C, washed with PBS, and
photographed. The antibody-blocking effect was dramatic; virtually no
antibody-treated neurons attached, in contrast to the large number of
cells that attached in untreated controls (Fig.
4, A and B). To be
sure that the blocking effect was specific, we tested the ability of
anti-IAP to interfere with neuronal binding to laminin. As shown in
Fig. 4, D and E, anti-IAP had no effect on
neuronal binding to laminin. Both P84 and IAP are found on a number of
non-neuronal tissues, with IAP found on lymphocytes and erythrocytes
(as well other tissues) and P84 found on dendritic cells and
macrophages (18, 19). To determine whether some of the other IAP
expressing cells could bind to P84, we tested thymocytes and
erythrocytes for their ability to bind to brain P84. Both erythrocytes
and thymocytes attached rapidly to P84-coated coverslips, and this
binding could be completely blocked by anti-IAP antibody (Fig. 4,
G-L). These experiments support the idea that
IAP might be a ubiquitous receptor for P84.

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Fig. 4.
Inhibition of cell attachment to P84 by
anti-IAP. Cerebellar neurons attach to immobilized P84 in the
absence of anti-IAP (A), but attachment is inhibited by
antibody (B). Neuronal attachment to laminin is unaffected
by absence (D) or presence (E) of anti-IAP.
Panel G demonstrates binding of erythrocytes, and
panel J demonstrates binding of thymocytes to P84 in the
absence of anti-IAP. This binding is completely blocked by anti-IAP as
shown in panels H and K, respectively. Cell
counts for each experiment are shown to the right in
panels C, F, I, and L. Asterisk
indicates values that differ significantly. Bar indicates 20 µM.
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P84 and IAP Have Nearly Identical Distributions in Synapse-rich
Regions of the Brain--
To be a functional ligand-receptor binding
pair in the brain, P84 and IAP must be expressed on adjacent membranes
of interacting cells. Previous studies with a P84 antibody demonstrated
an apparent synapse-associated distribution of P84 in cerebellum and
retina. We stained adjacent sections from these two structures with
anti-IAP and anti-P84 antibodies for comparison. The overall
distribution of P84 and IAP was strikingly similar. In the cerebellum,
the molecular layer exhibited the most intense P84 and IAP staining, and in the granule cell layer, staining was observed that appeared to
be associated with synaptic glomeruli (Fig.
5, A and B; see also Ref. 6). In the retina, both P84 and IAP were found in the
synapse-rich inner plexiform and outer plexiform layers, with little or
no staining outside of these synaptic layers (Fig. 5, C and
D). This co-localization of P84 and IAP is consistent with an adhesive association between these two molecules in
vivo.

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Fig. 5.
Co-localization of P84 and IAP in adult mouse
CNS. A, adult mouse retina was stained with anti-P84.
Arrowhead indicates outer plexiform layer, and
arrow indicates inner plexiform layer. B, retina
stained with anti-IAP shows a similar pattern to that seen in
panel A. C, mouse cerebellum shows intense
staining with anti-P84 in the molecular layer (M).
Structures within the granule cell layer (G) are also
stained. D, cerebellum stained with anti-IAP shows a pattern
similar to that seen in panel C. Bar indicates
0.1 mm.
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|
 |
DISCUSSION |
P84 is a synapse-associated cell adhesion molecule that is a
member of the immunoglobulin superfamily (5, 7). P84 is identical to
SHPS-1, BIT, and SIRP-
, molecules that are known to bind the
tyrosine phosphatase SHP-2 and modulate cell signaling (8-10). The
human SIRPs comprise a large family of signaling molecules, encoded by
different genes, with multiple isoforms generated from these genes by
alternative splicing (10). Because P84 has been associated with
synapse-rich regions in the CNS, and because P84 was known to bind to a
heterophilic receptor, the intriguing possibility existed that P84 and
its receptor were involved in establishment or regulation of synaptic
function. Isolation of a membrane ligand that bound to the
extracellular domain of P84 was critical for the analysis of mechanisms
by which P84 and this ligand contributed to the formation of synapses.
We have cloned a ligand for the P84 molecule and identified it as IAP
(CD 47). This identification is supported by the following observations. 1) The distribution of P84 binding activity (by RAP-in situ staining with P84-AP fusion protein) and IAP by
immunohistochemistry are identical. 2) The distribution of P84 and its
ligand, IAP, within the brain and retina are also identical, with both
being strongly expressed in various synaptic regions. 3) A monoclonal antibody against IAP completely blocked the attachment of cerebellar neurons, erythrocytes, and thymocytes to P84-coated substrates. These
findings support our conclusion that IAP was indeed a ligand for the
P84 adhesion molecule.
IAP was initially described as a 50-kDa cell surface protein that was
involved in the enhancement of neutrophil adhesion, chemotaxis, and
phagocytosis triggered by extracellular matrix molecules (20, 21). IAP
did not directly interact with integrin ligands (RGD-containing
peptides) but could physically associate with certain integrins and
could regulate integrin function (21). IAP appears to be a functional
component of several processes including (a)
transendothelial and transepithelial migration of neutrophils (23-25);
(b) integrin-mediated activation of neutrophils (14, 21);
(c) modulation of T-cell activation (26, 27); (d)
modulation of binding between integrins and ligands (24); (e) direct interaction between IAP and thrombospondins
(C-terminal cell binding domain) (28); and (f)
stroma-supported erythropoiesis in spleen and other tissues (17).
IAP was widely expressed in hematopoietic cells (erythrocytes,
lymphocytes, platelets, monocytes, and neutrophils) and other tissues
(placenta, surface epithelia, liver, and brain), including cells that
did not express integrins (29, 22). This suggested that there were
integrin-independent functions of IAP. The structure of human and
murine IAP was inferred from primary sequence of cloned cDNAs (30).
The N terminus of IAP (extracellular) contains an immunoglobulin-like
domain, most similar to members of the IgV family. Several
alternatively spliced isoforms of IAP mRNA are known to exist, one
of these (form 4) being most abundant in the brain and peripheral
nervous system (16). The human SIRP gene family contains at least 14 members that differ in the amino acid sequence of the extracellular
domains (10). Whether these different forms of P84/SIRP all bind to IAP
isoforms or to other ligands, remains to be determined.
Recently, an interesting correlation has been noted between levels of
IAP mRNA in the hippocampus and memory retention in rats (11).
These authors suggest that IAP may have a role in hippocampal synaptic
plasticity and memory formation, an idea consistent with our finding
that IAP is a ligand for the synaptic neural adhesion molecule, P84.
P84 homologues SHPS-1 and SIRP are known to be involved in cell
signaling via tyrosine phosphorylation in a variety of cell types. As
noted above, IAP is also known to play critical roles in cell signaling
in cells of the immune system. Our findings identify P84 and IAP as a
bi-directional signaling pair that may be preserved across a variety of
tissues, including both the nervous system and immune system. Although
the details of the mechanisms of signaling of each of these molecules
remains unclear, their distinct structures suggest that the signals are
likely to be different in the cells that express P84 and those that
express IAP. Based on their synaptic localization and apparent
signaling capacities, we propose that P84 and IAP may also be involved
in regulation of synaptic function and remodeling.
 |
ACKNOWLEDGEMENTS |
We thank Dr. J. Flanagan for providing the
Ap-tag plasmids and for sharing a manuscript describing AP-staining
methods. We thank Shari Olinsky and Jun Liu, for technical assistance,
and Dr. Pallavi Ishwad, for help at various stages.
 |
FOOTNOTES |
*
This work was supported by a grant from the National
Institutes of Health (to C. F. L. and V. N.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Rm. 7151 Rangos
Bldg., Children's Hospital of Pittsburgh, 3705 Fifth Ave. at DeSoto St., Pittsburgh, PA 15213. Tel.: 412-692-6078; Fax: 412-692-7824; E-mail: nara+{at}pitt.edu.
The abbreviations used are:
CNS, central nervous
system; IAP, integrin-associated protein (CD47); BCIP, 5-bromo-4-chloro-3-indolylphosphate p-toluidine salt; NBT, nitro blue tetrazolium chloride; AP, alkaline phosphatase; RAP, receptor alkaline phosphatase; PBS, phosphate-buffered saline; BSA, bovine serum albumin; FITC, fluorescein isothiocyanate; N-CAM, neural
cell adhesion molecule.
 |
REFERENCES |
-
Mayford, M.,
Barzilai, A.,
Keller, F.,
Schacher, S.,
and Kandel, E. R.
(1992)
Science
256,
638-644[Medline]
[Order article via Infotrieve]
-
Fannon, A. M.,
and Colman, D. R.
(1996)
Neuron
17,
423-434[Medline]
[Order article via Infotrieve]
-
Einheber, S.,
Schnapp, L. M.,
Salzer, J. L.,
Cappiello, Z. B.,
and Milner, T. A.
(1996)
J. Comp. Neurol.
370,
105-134[CrossRef][Medline]
[Order article via Infotrieve]
-
Hsueh, Y. P.,
Yang, F. C.,
Kharazia, V.,
Naisbitt, S.,
Cohen, A. R.,
Weinberg, R. J.,
and Sheng, M.
(1998)
J. Cell Biol.
142,
139-151[Abstract/Free Full Text]
-
Chuang, W.,
and Lagenaur, C. F.
( 1990)
Dev. Biol.
137,
219-232[Medline]
[Order article via Infotrieve]
-
Abosch, A.,
and Lagenaur, C.
(1993)
J. Neurobiol.
24,
344-355[Medline]
[Order article via Infotrieve]
-
Comu, S.,
Weng, W.,
Olinsky, S.,
Ishwad, P.,
Mi, Z.,
Hempel, J.,
Watkins, S.,
Lagenaur, C. F.,
and Narayanan, V.
(1997)
J. Neuroscience
17,
8702-8710[Abstract/Free Full Text]
-
Fujioka, Y.,
Matozaki, T.,
Noguchi, T.,
Iwamatsu, A.,
Yamao, T.,
Takahashi, N.,
Tsuda, M.,
Takada, T.,
and Kasuga, M.
(1996)
Mol. Cell. Biol.
16,
6887-6899[Abstract]
-
Sano, S.,
Ohnishi, H.,
Omori, A.,
Hasegawa, J.,
and Kubota, M.
(1997)
FEBS Lett.
411,
327-334[CrossRef][Medline]
[Order article via Infotrieve]
-
Kharitonenkov, A.,
Chen, Z.,
Sures, I.,
Wang, H.,
Schilling, J.,
and Ullrich, A.
(1997)
Nature
386,
181-186[CrossRef][Medline]
[Order article via Infotrieve]
-
Huang, A-M.,
Wang, H. L.,
Tang, Y. P.,
and Lee, E. H. Y.
(1998)
J. Neurosci.
18,
4305-4313[Abstract/Free Full Text]
-
Flanagan, J. G.,
and Leder, P.
(1990)
Cell
63,
185-194[Medline]
[Order article via Infotrieve]
-
Cheng, H-J.,
and Flanagan, J. G.
( 1994)
Cell
79,
157-168[Medline]
[Order article via Infotrieve]
-
Lindberg, F. P.,
Bullard, D. C.,
Caver, T. E.,
Gresham, H. D.,
Beaudet, A. L.,
and Brown, E. J.
(1996)
Science
274,
795-798[Abstract/Free Full Text]
-
Schnitzer, J.,
and Schachner, M.
(1981)
J. Neuroimmunol.
1,
429-456[Medline]
[Order article via Infotrieve]
-
Reinhold, M. I.,
Lindberg, F. P.,
Plas, D.,
Reynolds, S.,
Peters, M. G.,
and Brown, E. J.
(1995)
J. Cell Sci.
108,
3419-3425[Abstract/Free Full Text]
-
Furusawa, T.,
Yanai, N.,
Hara, T.,
Miyajima, A.,
and Obinata, M.
(1998)
J. Biochem.
123,
101-106[Abstract]
-
Adams, S.,
van der Laan, L. J. W.,
Vernon-Wilson, E.,
de Lavalette, C. R.,
Döpp, E. A.,
Dijkstra, C. D.,
Simmons, D. L.,
and van den Berg, T. K.
(1998)
J. Immunol.
161,
1853-1859[Abstract/Free Full Text]
-
Timms, J. F.,
Carlberg, K.,
Gu, H.,
Chen, H.,
Kamatkar, S.,
Nadler, M. J. S.,
Rohrshneider, L. R.,
and Neel, B. G.
(1998)
Mol. Cell. Biol.
18,
3838-3850[Abstract/Free Full Text]
-
Senior, R. M.,
Gresham, H. D.,
Griffin, G. L.,
Brown, E. J.,
and Chung, A. E.
(1992)
J. Clin. Invest.
90,
2251-2257[Medline]
[Order article via Infotrieve]
-
Brown, E.,
Hooper, L.,
Ho, T.,
and Gresham, H.
( 1990)
J. Cell Biol
111,
2785-2794[Abstract]
-
Mawby, W. J.,
Holmes, C. H.,
Anstee, D. J.,
Spring, F. A.,
and Tanner, M. J. A.
(1994)
Biochem. J.
304,
525-530[Medline]
[Order article via Infotrieve]
-
Cooper, D.,
Lindberg, F. P.,
Gamble, J. R.,
Brown, E. J.,
and Vadas, M. A.
(1995)
Proc. Natl. Acad. Sci. U. S. A.
92,
3978-3982[Abstract/Free Full Text]
-
Lindberg, F. P.,
Gresham, H. D.,
Reinhold, M. I.,
and Brown, E. J.
(1996)
J. Cell Biol.
134,
1313-1322[Abstract]
-
Parkos, C. A.,
Colgan, S. P.,
Liang, T. W.,
Nusrat, A.,
Bacarra, A. E.,
Carnes, D. K.,
and Madara, J. L.
(1996)
J. Cell Biol.
132,
437-450[Abstract]
-
Waclavicek, M.,
Majdic, O.,
Stulnig, T.,
Berger, M.,
Baumruker, T.,
Knapp, W.,
and Pickl, W. F.
(1997)
J. Immunol.
159,
5345-5354[Abstract]
-
Ticchioni, M.,
Deckert, M.,
Mary, F.,
Bernard, G.,
Brown, E. J.,
and Bernard, A.
(1997)
J. Immunol.
158,
677-684[Abstract]
-
Gao, A-G.,
Lindberg, F. P.,
Finn, M. B.,
Blystone, S. D.,
Brown, E. J.,
and Frazier, W. A.
(1996)
J. Biol. Chem.
271,
21-24[Abstract/Free Full Text]
-
Rosales, C.,
Gresham, H. D.,
and Brown, E. J.
(1992)
J. Immunol.
149,
2759-2764[Abstract/Free Full Text]
-
Lindberg, F. P.,
Gresham, H. D.,
Schwarz, E.,
and Brown, E. J.
(1993)
J. Cell Biol.
123,
485-496[Abstract]
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.