MDC-L, a Novel Metalloprotease Disintegrin Cysteine-rich Protein Family Member Expressed by Human Lymphocytes

Abstract

The metalloprotease disintegrin cysteine-rich (MDC) proteins are a recently identified family of transmembrane proteins that function in proteolytic processing of cell surface molecules and in cell adhesion. Since lymphocytes must interact with a constantly changing environment, we hypothesized that lymphocytes would express unique MDC proteins. To identify MDC proteins expressed in human lymph node, a polymerase chain reaction-based strategy combined with degenerate oligonucleotide primers was employed. We report here the identification of MDC-L (ADAM 23), a novel member of the MDC protein family. The results obtained from cDNA cloning and Northern blot analysis of mRNA isolated from various lymphoid tissues indicate that a 2.8-kilobase mRNA encoding a transmembrane form, MDC-Lm, and a 2.2-kilobase mRNA encoding a secreted form, MDC-Ls, are expressed in a tissue-specific manner. MDC-L mRNA was shown to be predominantly expressed in secondary lymphoid tissues, such as lymph node, spleen, small intestine, stomach, colon, appendix, and trachea. Furthermore, immunohistochemical staining with an anti-MDC-L antibody demonstrated that cells with typical lymphocyte morphology are responsible for expression of the MDC-L antigen in these lymphoid tissues. MDC-Lm was found to be expressed on the surface of human peripheral blood lymphocytes and transformed B- and T-lymphocyte cell lines as an 87-kDa protein. Thus, we have identified a novel lymphocyte-expressed MDC protein family member. The metalloprotease disintegrin cysteine-rich (MDC) proteins are a recently identified family of transmembrane proteins that function in proteolytic processing of cell surface molecules and in cell adhesion. Since lymphocytes must interact with a constantly changing environment, we hypothesized that lymphocytes would express unique MDC proteins. To identify MDC proteins expressed in human lymph node, a polymerase chain reaction-based strategy combined with degenerate oligonucleotide primers was employed. We report here the identification of MDC-L (ADAM 23), a novel member of the MDC protein family. The results obtained from cDNA cloning and Northern blot analysis of mRNA isolated from various lymphoid tissues indicate that a 2.8-kilobase mRNA encoding a transmembrane form, MDC-Lm, and a 2.2-kilobase mRNA encoding a secreted form, MDC-Ls, are expressed in a tissue-specific manner. MDC-L mRNA was shown to be predominantly expressed in secondary lymphoid tissues, such as lymph node, spleen, small intestine, stomach, colon, appendix, and trachea. Furthermore, immunohistochemical staining with an anti-MDC-L antibody demonstrated that cells with typical lymphocyte morphology are responsible for expression of the MDC-L antigen in these lymphoid tissues. MDC-Lm was found to be expressed on the surface of human peripheral blood lymphocytes and transformed B- and T-lymphocyte cell lines as an 87-kDa protein. Thus, we have identified a novel lymphocyte-expressed MDC protein family member. metalloprotease disintegrin cysteine-rich protein a disintegrin and metalloprotease epidermal growth factor matrix metalloprotease tissue necrosis factor-α-converting enzyme polymerase chain reaction 5′-rapid amplification of cDNA ends reverse transcriptase polyacrylamide gel electrophoresis kilobase(s) base pair(s) phosphate-buffered saline fetal calf serum N-tris(hydroxymethyl)methylglycine MDC,1 or ADAMs, are a family of transmembrane glycoproteins with a unique domain structure (1Blobel C.P. Cell. 1997; 90: 589-592Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar, 2Wolfsberg T.G. White J.M. Dev. Biol. 1996; 180: 389-401Crossref PubMed Scopus (217) Google Scholar). The prototypical MDC protein comprises pro, metalloprotease, disintegrin, cysteine-rich, EGF, transmembrane, and cytoplasmic domains. The metalloprotease domain is homologous to the reprolysins, members of the zinc binding metzincin superfamily that also includes the matrix metalloproteases (MMPs), the astacins, and serralysins (3Stocker W. Grams F. Baumann U. Reinemer P. Gomis-Ruth F.-X. McKay D.B. Bode W. Protein Sci. 1995; 4: 823-840Crossref PubMed Scopus (638) Google Scholar). The prodomain regulates the activity of the metalloprotease by blocking access to the zinc ion; removal of the prodomain or inactivation of a conserved cysteine thiol group results in a gain of proteolytic activity. The disintegrin domains of MDC proteins are homologous to small nonenzymatic peptides isolated from the venom of snakes. Snake venom disintegrin peptides interfere with platelet aggregation by inhibiting binding of fibrinogen to the integrin αIIbβ3 (4Niewiarowski S. McLane M.A. Kloczewiak M. Stewart G.J. Semin. Hematol. 1994; 31: 289-300PubMed Google Scholar). The functions previously attributed to the individual domains suggests roles for MDC proteins in cell adhesion and the proteolysis of extracellular proteins. The first mammalian MDC proteins identified were the fertilins (5Blobel C.P. Wolfsberg T.G. Turck C.W. Myles D.G. Primakoff P. White J.M. Nature. 1992; 356: 248-252Crossref PubMed Scopus (612) Google Scholar). These proteins function in the attachment and fusion of the sperm and egg during fertilization. A similar cell fusion function for the MDC protein meltrin-α (MDC-12) was shown for the formation of multinucleated myotubes (6Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y.-i. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (439) Google Scholar). These MDC proteins have, in addition to the domains described above, a fusion peptide-like sequence not found in all members of the MDC protein family. However, the interaction of the fertilin disintegrin domain on the sperm surface with the integrin α6β1 on the surface of the egg is also required for membrane adhesion and fusion (7Myles D.G. Kimmel L.H. Blobel C.P. White J.M. Primakoff P. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 4195-4198Crossref PubMed Scopus (233) Google Scholar, 8Yuan R. Primakoff P. Myles D.G. J. Cell Biol. 1997; 137: 105-112Crossref PubMed Scopus (203) Google Scholar, 9Almeida E.A.C. Huovila A.-P.J. Sutherland A.E. Stephens L.E. Calarco P.G. Shaw L.M. Mercurio A.M. Sonnenberg A. Primakoff P. Myles D.G. White J.M. Cell. 1995; 81: 1095-1104Abstract Full Text PDF PubMed Scopus (471) Google Scholar). Additional evidence for the functionality of the disintegrin domain comes from studies using recombinantly expressed metargidin (MDC-15) disintegrin domain, which was shown to specifically interact with the integrin αvβ3 (10Zhang X.-P. Kamata T. Yokoyama K. Puzon-Mclaughlin W. Takada Y. J. Biol. Chem. 1998; 273: 7345-7350Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar). Thus, the disintegrin domains of MDC proteins appear to be a new family of integrin ligands. More recently, MDC proteins have been shown to function in ectodomain shedding of several cell surface proteins. Tissue necrosis factor-α converting enzyme (TACE; MDC-17) was the first mammalian MDC protein shown to have secretase activity (11Black R.A. Rauch C.T. Kozlosky C.J. Peschon J.J. Slack J.L. Wolfson M.F. Castner B.J. Stocking K.L. Reddy P. Srinivasan S. Nelson N. Boiani N. Schooley K.A. Gerhart M. Davis R. Fitzner J.N. Johnson R.S. Paxton R.J. March C.J. Cerretti D.P. Nature. 1997; 385: 729-733Crossref PubMed Scopus (2728) Google Scholar, 12Moss M.L. Jin S.-L.C. Milla M.E. Burkhart W. Carter H.L. Chen W.-J. Clay W.C. Didsbury J.R. Hassler D. Hoffman C.R. Kost T.A. Lambert M.H. Leesnitzer M.A. McCauley P. McGeehan G. Mitchell J. Moyer M. Pahel G. Rocque W. Overton L.K. Schoenen F. Seaton T. Su J.-L. Warner J. Willard D. Becherer J.D. Nature. 1997; 385: 733-736Crossref PubMed Scopus (1490) Google Scholar, 13Peschon J.J. Slack J.L. Reddy P. Stocking K.L. Sunnarborg S.W. Lee D.C. Russell W.E. Castner B.J. Johnson R.S. Fitzner J.N. Boyce R.W. Nelson N. Kozlosky C.J. Wolfson M.F. Rauch C.T. Cerretti D.P. Paxton R.J. March C.J. Black R.A. Science. 1998; 282: 1281-1284Crossref PubMed Scopus (1371) Google Scholar). Additionally, meltrin-γ (MDC-9) is involved in ectodomain shedding of membrane anchored heparin-binding EGF-like growth factor, and considerable evidence supports the proteolytic processing of notch by theDrosophila MDC protein Kuzbian (14Izumi Y. Hirata M. Hasuwa H. Iwamoto R. Umata T. K. Y. Kurisaki T. A. S. J. 1998; PubMed Scopus Google Scholar, J. D. T. Science. 1996; Scopus Google Scholar, D. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, H. N. W. P. T. S. Science. PubMed Scopus Google Scholar). proteins are from cell by MDC proteins in proteolytic processing J. 1997; PubMed Scopus Google Scholar). Thus, MDC proteins function in a of the of from the cell surface as in the of tissue necrosis MDC proteins by or from the cell such as in the shedding of J. F. J. Cell Biol. 1994; PubMed Scopus Google Scholar, K. J. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). the and MDC proteins suggests a in extracellular matrix MDC protein function as for integrin The here a novel member of the MDC protein expressed by lymphocytes in the tissues encoding a prototypical MDC protein and the encoding a secreted form, demonstrated tissue The transmembrane of MDC-L was expressed as an 87-kDa protein on the surface of peripheral blood lymphocytes and B- and T-lymphocyte cell We that MDC-L a in the and proteolytic that during lymphocyte or function in ectodomain shedding of lymphocyte proteins such as or an as lymphocyte protein M. T. M. S. 1998; 4: PubMed Scopus Google Scholar, F. S. H. G. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). The T-lymphocyte cell was obtained from H. and in fetal calf serum H. A. J. 1997; PubMed Google Scholar). The cell was by W. of and in The T-lymphocyte cell was obtained from and in of was by J. T. A Scholar). and were from were by the the of The degenerate oligonucleotide primers were and in which A or and or G. Blobel C.P. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar). was as reaction of human lymph cDNA was combined with of primers and in a using the The were from the by reaction the reaction were combined with of primers and in a The obtained from reaction were and the sequence of A from a MDC-L was from a polyacrylamide gel and with by the removal of the the was to a human lymph cDNA were a and all the on a were The cDNA from the were of a with and reverse primers J. Lee P. H. M. Google Scholar). The sequence of was using and The amplification of cDNA ends was using cDNA as by with the primers and the The obtained were from the primers by and to a with the primers and The obtained was and using and The tissue and mRNA blot were from of the mRNA blot was with the for cDNA The was a from the of MDC-Lm cDNA that been from an The was a from the of were with by the to a activity to were with the as described W. G. S. Google Scholar). The were to for of the to the was by for in in and was using the mRNA and and the for of human lymph mRNA were and blood were isolated by human blood with and and the cells with a The isolated cells were and cells were for for were and was using a reaction with of the reaction as and the primers and The were by gel electrophoresis and with the The MDC-L disintegrin domain was from the with the and with the expression and transformed the MDC-L disintegrin domain were in and to of was to a of and the cells were for The cell was for and the was in and The cell was for the in and on to the was with and with the The fusion protein was in phosphate-buffered saline and by The was by The MDC-Lm domain was from the with the and with and and the fusion fusion proteins were and as described S. M. M.H. J. Biol. Chem. Full Text PDF PubMed Google Scholar). the of were with disintegrin domain or domain fusion proteins D. Scholar). was obtained by protein anti-MDC-L disintegrin domain antibody was obtained by of with the disintegrin domain with and with antibody was with and in was and Nature. PubMed Scopus Google Scholar). were by the of proteins to blocking in and with a The antibody was by with a secondary with and by blood lymphocytes were isolated from by cell were by cell in were by surface of cells with of in for The cells were in and on for in of for of the was with of protein with the for on The was with in to to and proteins as described tissues were obtained from of or from and of the of and were to were in and using and were to antigen tissues. Tissue were as described K.L. 1996; PubMed Google Scholar). were with in for to activity. staining for MDC-L antigen was using The were with serum to antibody by addition of the antibody in serum for secondary antibody was for by for was as was for Protein were by the The MDC-L disintegrin domain was by of disintegrin domain in to of The matrix was in for several with and and in base were using the for sequence were using the protein N. 1997; PubMed Scopus Google Scholar). To lymphocytes express MDC protein family human lymph cDNA was to of with of degenerate oligonucleotide These degenerate primers were on the sequence of conserved the disintegrin domains of MDC proteins G. Blobel C.P. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar). A was obtained the secondary The were and the the were encoding the disintegrin domains of human (6Yagami-Hiromasa T. Sato T. Kurisaki T. Kamijo K. Nabeshima Y.-i. Fujisawa-Sehara A. Nature. 1995; 377: 652-656Crossref PubMed Scopus (439) Google Scholar, G. J. Blobel C.P. J. Cell Biol. 1996; PubMed Scopus Google and R. 1998; PubMed Scopus Google However, of the an encoding a unique with to of the and venom base using J. 1996; PubMed Google that novel disintegrin domain was to the disintegrin domains of human sperm and the protein and These results that a novel MDC family which we have MDC-L (ADAM 23), be expressed the human lymph the isolated cDNA encoding the MDC-L disintegrin domain as a a human lymph cDNA was and were The cDNA from that were and the sequence of these the of the MDC-L the MDC-L cDNA was by using human lymph The cDNA obtained in the of with the cDNA sequence was found in base using The cDNA an encoding a with the typical domain structure of MDC family a as as pro, metalloprotease, disintegrin, cysteine-rich, EGF, and transmembrane domains (1Blobel C.P. Cell. 1997; 90: 589-592Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar, G. Blobel C.P. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar, T.G. Huovila A.-P.J. Primakoff P. Myles D.G. White J.M. Dev. Biol. 1995; PubMed Scopus Google Scholar, T.G. Primakoff P. Myles D.G. White J.M. J. Cell Biol. 1995; PubMed Scopus Google We have transmembrane protein MDC-Lm The cDNA an encoding a protein with a pro, metalloprotease, and disintegrin domains to the MDC-Lm the cysteine-rich domain in sequence and a secreted of protein been MDC-L cDNA M. PubMed Scopus Google and M. T. Cell. Full Text PDF PubMed Scopus Google that these are and of of the domain of MDC-Lm and The sequence prodomain metalloprotease disintegrin domain cysteine-rich domain domain transmembrane domain and cytoplasmic domain are shown are the zinc binding and integrin of the MDC-L that the metalloprotease domain the which the for zinc and the (3Stocker W. Grams F. Baumann U. Reinemer P. Gomis-Ruth F.-X. McKay D.B. Bode W. Protein Sci. 1995; 4: 823-840Crossref PubMed Scopus (638) Google Scholar). demonstrated that the required for zinc and all be the structure not The prodomain also a found in R. S. J. 1998; PubMed Scopus Google Scholar). The sequence the the prodomain and the metalloprotease sequence not with the enzyme identified in MDC and family members R. S. J. 1998; PubMed Scopus Google Scholar). The disintegrin domain the sequence the integrin T.G. White J.M. Dev. Biol. 1996; 180: 389-401Crossref PubMed Scopus (217) Google Additionally, the MDC-Lm protein the The identified that MDC-L a metalloprotease and a integrin from several lymphoid tissues were for expression of MDC-Lm and shown in an mRNA of in lymph and to the MDC-Lm also a mRNA in the peripheral blood mRNA not the blot was with a for MDC-Ls, a was in not in lymph or the tissues Since the cDNA was isolated from lymph node, mRNA from tissue was in a analysis using to and for MDC-L shown in of the were in and was by unique to MDC-L cDNA not from the Northern blot the MDC-Lm mRNA to be These results indicate that of MDC-L mRNA are expressed in a tissue-specific manner. The results obtained to the tissue of MDC-L isolated from human tissues were by mRNA with a to MDC-L MDC-L mRNA was predominantly expressed in secondary lymphoid tissues expression was in of the fetal tissues or with the of the A of the MDC-L cDNA with the identified a of that from the MDC-L Thus, we that the of the MDC-L with the was Since MDC-L mRNA to be for secondary lymphoid tissues, we that was the lymphocyte in these tissues that express blood were for the of MDC-Lm and was to and cells from of these was by for the of MDC-Lm and mRNA and and expressed MDC-Lm and MDC-L mRNA was also in the and Northern blot analysis that MDC-Lm mRNA was in peripheral blood results from indicate that mRNA from of MDC-L are MDC-L protein expression in peripheral blood lymphocytes was by cell with an anti-MDC-L disintegrin domain of and were specifically results were obtained the 87-kDa These from the cDNA and However, these results not the protein was the protein or a of the MDC-Lm protein the These results indicate that the MDC-Lm, and the MDC-Ls, proteins are expressed by peripheral blood To which cell the lymphoid tissue were the MDC-L the anti-MDC-L disintegrin domain was for immunohistochemical staining of from human lymph node, small intestine, colon, stomach, spleen, and The results for lymph node, small intestine, and are shown in with typical lymphocyte morphology were specifically by the anti-MDC-L antibody in all the tissues The of the lymph MDC-L lymphocytes were in the and a cells were the were also found in of the and the of lymphocytes that were to be in these tissues with lymph and not lymphocytes of the small and were found and the of staining of lymphocytes in the and lymphoid These results that a of the lymphocyte was specifically by the Since the and immunohistochemical studies that and were the lines and as as the were for the expression of A protein of was specifically in all cell lines by an anti-MDC-L disintegrin domain in of cell A protein of was also specifically from cells The of the domain antibody was by and of an 87-kDa protein with a antibody that the domain of MDC-L specifically protein in of the cell or human cells not These indicate in the transformed and express the transmembrane of MDC-L on the cell a novel member of the MDC protein which we have MDC-L (ADAM of expression in human that a transmembrane, MDC-Lm, and MDC-Ls, of the protein were MDC-L mRNA was predominantly to secondary lymphoid tissues, and demonstrated that the lymphocyte was responsible for MDC-L expression in these tissues. A using degenerate was to identify MDC protein family members expressed in human lymph domain by and were the of the the disintegrin domain of is to that MDC-L is the MDC protein expressed by such as to for a cDNA disintegrin domain proteins not have shown in MDC family members have been shown to be expressed lymph and G. R.A. J. 1998; Google Scholar, S. F. S. J. 1997; PubMed Scopus Google Scholar). which is expressed by a disintegrin domain and not have a typical MDC protein domain The disintegrin domain of the conserved in the of the degenerate Thus, would not have been to a the in (11Black R.A. Rauch C.T. Kozlosky C.J. Peschon J.J. Slack J.L. Wolfson M.F. Castner B.J. Stocking K.L. Reddy P. Srinivasan S. Nelson N. Boiani N. Schooley K.A. Gerhart M. Davis R. Fitzner J.N. Johnson R.S. Paxton R.J. March C.J. Cerretti D.P. Nature. 1997; 385: 729-733Crossref PubMed Scopus (2728) Google Scholar, 12Moss M.L. Jin S.-L.C. Milla M.E. Burkhart W. Carter H.L. Chen W.-J. Clay W.C. Didsbury J.R. Hassler D. Hoffman C.R. Kost T.A. Lambert M.H. Leesnitzer M.A. McCauley P. McGeehan G. Mitchell J. Moyer M. Pahel G. Rocque W. Overton L.K. Schoenen F. Seaton T. Su J.-L. Warner J. Willard D. Becherer J.D. Nature. 1997; 385: 733-736Crossref PubMed Scopus (1490) Google Scholar). is not was identified in protein is a expressed secretase (14Izumi Y. Hirata M. Hasuwa H. Iwamoto R. Umata T. K. Y. Kurisaki T. A. S. J. 1998; PubMed Scopus Google Scholar). was previously as a protein R. 1998; PubMed Scopus Google Scholar). The of here be to of the cDNA or expression of tissues such as human lymph MDC-Lm a prototypical MDC or family domain for zinc binding and activity were that MDC-L have a proteolytic MDC proteins have been shown to have an and function in ectodomain shedding (11Black R.A. Rauch C.T. Kozlosky C.J. Peschon J.J. Slack J.L. Wolfson M.F. Castner B.J. Stocking K.L. Reddy P. Srinivasan S. Nelson N. Boiani N. Schooley K.A. Gerhart M. Davis R. Fitzner J.N. Johnson R.S. Paxton R.J. March C.J. Cerretti D.P. Nature. 1997; 385: 729-733Crossref PubMed Scopus (2728) Google Scholar, 12Moss M.L. Jin S.-L.C. Milla M.E. Burkhart W. Carter H.L. Chen W.-J. Clay W.C. Didsbury J.R. Hassler D. Hoffman C.R. Kost T.A. Lambert M.H. Leesnitzer M.A. McCauley P. McGeehan G. Mitchell J. Moyer M. Pahel G. Rocque W. Overton L.K. Schoenen F. Seaton T. Su J.-L. Warner J. Willard D. Becherer J.D. Nature. 1997; 385: 733-736Crossref PubMed Scopus (1490) Google Scholar, Y. Hirata M. Hasuwa H. Iwamoto R. Umata T. K. Y. Kurisaki T. A. S. J. 1998; PubMed Scopus Google Scholar, D. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google activity Mitchell S. S. P. J. 1996; PubMed Scopus Google Scholar, S. N. 1998; PubMed Scopus Google and meltrin-α (MDC-12) F. B.J. R. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). The metalloprotease domain of MDC-L was homologous to the metalloproteases and found in the venom and J.R. M. C.R. 1994; Scholar, Full Text PDF PubMed Scopus Google Scholar). Since of these venom metalloproteases have the MDC-L metalloprotease have a activity. However, a in ectodomain shedding of a lymphocyte surface such as or not been MDC-L also a sequence for a cysteine found to proteolytic activity in MDC and protein family However, MDC-L not a sequence for a the also a sequence for that for removal of the prodomain for MDC-L R. S. J. 1998; PubMed Scopus Google Scholar). The sequence here that MDC-L be as a that Snake venom disintegrin peptides function as of integrin function (4Niewiarowski S. McLane M.A. Kloczewiak M. Stewart G.J. Semin. Hematol. 1994; 31: 289-300PubMed Google Scholar, M.A. S. S. Biol. 1998; PubMed Scopus Google Scholar). The integrin in several of these disintegrin peptides been to an sequence an of the of mammalian MDC disintegrin domains been demonstrated for and the fertilins (7Myles D.G. Kimmel L.H. Blobel C.P. White J.M. Primakoff P. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 4195-4198Crossref PubMed Scopus (233) Google Scholar, 9Almeida E.A.C. Huovila A.-P.J. Sutherland A.E. Stephens L.E. Calarco P.G. Shaw L.M. Mercurio A.M. Sonnenberg A. Primakoff P. Myles D.G. White J.M. Cell. 1995; 81: 1095-1104Abstract Full Text PDF PubMed Scopus (471) Google Scholar, X.-P. Kamata T. Yokoyama K. Puzon-Mclaughlin W. Takada Y. J. Biol. Chem. 1998; 273: 7345-7350Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar). the of an sequence a similar to that of the venom peptides is by the integrin αvβ3 (10Zhang X.-P. Kamata T. Yokoyama K. Puzon-Mclaughlin W. Takada Y. J. Biol. Chem. 1998; 273: 7345-7350Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar). A from the the disintegrin domain, been shown to adhesion and cell fusion (7Myles D.G. Kimmel L.H. Blobel C.P. White J.M. Primakoff P. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 4195-4198Crossref PubMed Scopus (233) Google Scholar, 8Yuan R. Primakoff P. Myles D.G. J. Cell Biol. 1997; 137: 105-112Crossref PubMed Scopus (203) Google Scholar). suggests that is blocking sperm binding to the egg integrin α6β1 E.A.C. Huovila A.-P.J. Sutherland A.E. Stephens L.E. Calarco P.G. Shaw L.M. Mercurio A.M. Sonnenberg A. Primakoff P. Myles D.G. White J.M. Cell. 1995; 81: 1095-1104Abstract Full Text PDF PubMed Scopus (471) Google Scholar). MDC-L a sequence similar to that found in the that MDC-L also be by the integrin MDC-L were identified in These from or The for of MDC protein family member to the results shown here for is also expressed as transmembrane and secreted B.J. F. R. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). MDC-L and with to the of the transmembrane and secreted The of MDC-L the cysteine-rich domain, the the of the transmembrane MDC-Lm and were to in tissue was expressed in spleen, also be in lymph using suggests that of the of MDC-L unique and results that MDC-Lm is expressed by peripheral blood lymphocytes of these results are the in mRNA expression in lymphoid tissues suggests that MDC-L expression be during or lymphocyte The results demonstrated the of MDC-Lm and in peripheral blood and MDC-Lm mRNA was in the and These results that express the and which are predominantly of and also and studies are required to MDC-Lm expression on the surface of peripheral blood MDC-Lm was expressed as an 87-kDa protein on the surface of and cell lines and peripheral blood The of MDC-Lm was by and with a anti-MDC-L domain Since domain was not in MDC-Ls, the anti-MDC-L would be to specifically the MDC-Lm protein. a protein of was with anti-MDC-L disintegrin domain and anti-MDC-L that MDC-Lm not with lymphocyte cell surface proteins. to a secreted of MDC-L from or from human were not we were to of the blood lymphocytes express a anti-MDC-L disintegrin domain protein. was a of MDC-Lm the prodomain or was not are members of the MDC or protein family. the in function of a have been the roles are and to the and of an of the first identified roles for MDC proteins was in These MDC proteins all a fusion which was not in of the MDC-L cDNA (5Blobel C.P. Wolfsberg T.G. Turck C.W. Myles D.G. Primakoff P. White J.M. Nature. 1992; 356: 248-252Crossref PubMed Scopus (612) Google Scholar). However, not a in cell adhesion for The identification of an MDC protein expressed by lymphocytes suggests that MDC-L have an is from the surface of by an metalloprotease, and been to function in of cells from M. T. M. S. 1998; 4: PubMed Scopus Google Scholar). metalloprotease is also in the shedding of from the surface of F. S. H. G. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). MDC-L also function in a similar to which are required for of lymphocytes from the The expression in that MDC-L is expressed by and the of anti-MDC-L and the lymphocyte surface be to the and expression of the in function of novel MDC protein. We and for and on the We also M. for