CD44 is an integral cell membrane glycoprotein with a postulated role in matrix adhesion lymphocyte activation and lymph node homing.

"CD44" "is an" "integral cell membrane glycoprotein"
"CD44"" has a postulated role in" "matrix adhesion lymphocyte activation"
"CD44"" has a postulated role in" "lymph node homing"

The nucleotide sequence of CD44 cDNAs predicts a 37-kD polypeptide with homology to cartilage link protein (115435) in a phylogenetically conserved amino-terminal domain.

"CD44 cDNAs"" is" "a nucleotide sequence"
"CD44 cDNAs" "predicts" "a 37-kD polypeptide with homology to cartilage link protein (115435) in a phylogenetically conserved amino-terminal domain"

Aruffo et al. (1990) demonstrated that CD44 is the main cell surface receptor for hyaluronate.

"CD44" "is the main cell surface receptor for" "hyaluronate"
"Aruffo et al. (1990)" "demonstrated" "that"

Mature lymphocytes in the circulation migrate selectively from the bloodstream to different lymphatic tissues through specialized high endothelial venules (HEV

"Mature lymphocytes in the circulation" "migrate selectively from" "the bloodstream"
"Mature lymphocytes in the circulation" "migrate selectively to " " different lymphatic tissues"
"Mature lymphocytes in the circulation" "migrate through" "specialized high endothelial venules (HEV)"

Molecules on the surface of lymphocytes called homing receptors interact specifically with HEV and play a central role in the migration.

"Molecules"" are on the surface of lymphocytes"
"These molecules" "are called" "homing receptors"
"These molecules" "interact specifically with" "HEV"
"These molecules""play a central role in" "the migration"

The mouse monoclonal antibody Hermes-3 recognizes the 85-95 kD human lymphocyte homing receptor.

"Hermes-3" "is a" "mouse monoclonal antibody"
" Hermes-3" "recognizes" "the 85-95 kD human lymphocyte homing receptor"

Using mouse-human T-lymphocyte hybrids and hybrids of Chinese hamster ovary cells with human amniotic fibroblasts, Ala-Kapee et al. (1989) found that Hermes-3 expression, as demonstrated by indirect immunofluorescence and immunoprecipitation, was determined by 11pter-p13.

"Ala-Kapee et al (1989)." "found" "Hermes-3 expression"
"Ala-Kapee et al." " used" " mouse-human T-lymphocyte hybrids"
"Ala-Kapee et al." " used" "hybrids of Chinese hamster ovary cells with human amniotic fibroblast"
"Hermes-3 expression"" was determined by" "11pter-p13"
"Hermes-3 expression"" was demonstrated by"" indirect immunofluorescence"
"Hermes-3 expression"" was demonstrated by" "immunoprecipitation"

Forsberg et al. (1989) refined the assignment of the lymphocyte homing receptor gene to 11pter-p13 by study of Chinese hamster-human cell hybrids in which the human parent cells had various deletions of human chromosome 11.

"Forsberg et al. (1989)" "refined the assignment of" "the lymphocyte homing receptor gene"
"The lymphocyte homing receptor gene" "is assigned to" "11pter-p13"
"Assignment " "was refined by study of" "Chinese hamster-human cell hybrids"
"Chinese hamster-human cell hybrids" "contained" "human parent cells"
"Human parent cells" "had various deletions of" "human chromosome 11"

Stefanova et al. (1989) demonstrated that the lymphocyte homing receptor is identical to the human leukocyte surface glycoprotein called CDw44, on the basis of studies at the Third International Workshop on Human Leukocyte Differentiation Antigens.

"the lymphocyte homing receptor" "is identical to" "the human leukocyte surface glycoprotein"
"Stefanova et al. (1989)" "demonstrated" "sameness"
"the human leukocyte surface glycoprotein" "is called" "CDw44"
"studies" "were conducted at" "the Third International Workshop on Human Leukocyte Differentiation Antigens."

It also appears to be identical to the Pgp-1 glycoprotein of Omary et al. (1988).

"the lymphocyte homing receptor" "also appears to be identical"" to the Pgp-1 glycoprotein of Omary et al. (1988)" THIS DOES NOT MAKE SENSE TO ME

Telen et al. (1983) used a murine monoclonal antibody (A3D8) to identify an erythrocyte antigen inhibited by the In(Lu) gene.

"Telen et al. (1983)" "identified" "an erythrocyte antigen"
"The erythrocyte antigen" "is inhibited by" "the In(Lu) gene"
"Telen et al. (1983)" "used" "a murine monoclonal antibody (A3D8)"

Telen et al. (1984) showed that the A3D8 antigenic property resides on an 80-kD red cell membrane protein which is present in only trace amounts in In(Lu) Lu(a-b-) red cells (INLU; 111150).

"Telen et al. (1984)" "showed residence of" "A3D8 antigenic property"
" the A3D8 antigenic property" "resides on" "an 80-kD red cell membrane protein"
"The 80-kD red cell membrane protein" "is present in" "only trace amounts"
"The 80-kD red cell membrane protein" "is present in" "In(Lu) Lu(a-b-) red cells (INLU; 111150)"

Francke et al. (1983) showed that the antigens defined by monoclonal antibodies A3D8 and A1G3 are determined by genes on 11p.

"Francke et al. (1983)" showed" "determination"
"monoclonal antibody A3D8" "defines "antigens"
"monoclonal antibody A1G3" "defines" "antigens"
" genes on 11p" "determine" "antigens"

Haynes (1986) had evidence that the A1G3 and A3D8 monoclonal antibodies bind to different epitopes on the same 80-kD molecule.

"Haynes (1986)" "had" "evidence"
"A1G3" "is " "a monoclonal antibody"
"A3D8" "is" "a monoclonal antibody"
"A1G3" "binds to" " different epitopes"
"A3D8" "binds to" "different epitopes"
"different epitopes" "are on" "the same 80-kD molecule"

The monoclonal antibody A3D8 recognized an antigen officially called MDU3--'monoclonal Duke University, 3,' or CD44.

"A3D8" "recognized" "an antigen"
"antigen" "is called" "MDU3--'monoclonal Duke University, 3,'"
"MDU3--'monoclonal Duke University, 3,'" "is also called" "CD44"

Telen (1992) knew of no evidence that the INLU and CD44 (MDU3) genes are the same.

"Telen (1992)" "did not" "know"
"INLU" "is the same as" "CD44 (MDU3)"

Cianfriglia et al. (1992) mapped a drug-sensitivity marker, MC56, to 11pter-p13.

Cianfriglia et al. (1992)" "mapped" "MC56"
"MC56" "is" "a drug-sensitivity marker"
" MC56," "is mapped to" "11pter-p13"

Identity of the protein to the CD44 antigen, suggested on other grounds, was supported by the map location.

"Identity of the protein to the CD44 antigen "was supported by" "the map location"

Although CD44 may have function as a lymphocyte homing receptor, the gene that maps to chromosome 11 is distinct from the lymph node homing receptor located on chromosome 1 (153240) (Seldin, 1990).

"CD44" "may have function as" "a lymphocyte homing receptor"
"the gene that maps to chromosome 11" "is distinct from" "the lymph node homing receptor"
"the lymph node homing receptor" "is located on" "chromosome 1 (153240)"

In the mouse, the corresponding gene has been referred to as Ly-24.

"the corresponding mouse gene" "has been referred to" "as Ly-24"

Screaton et al. (1992) found that the CD44 gene contains 19 exons spanning some 50 kb of genomic DNA.

Screaton et al. (1992) found that
" the CD44 gene" "contains" "19 exons"
"the 19 exons" span" "some 50 kb of genomic DNA"

They identified 10 alternatively spliced exons within the extracellular domain, including 1 exon that had not previously been reported.

"10 alternatively spliced exons" "were identified" "within the extracellular domain"
"1 exon" "had not previously been" "reported"

In addition to the inclusion or exclusion of whole exons, additional diversity was generated through the utilization of internal splice donor and acceptor sites within 2 of the exons.

"whole exons" "have been""included"
"whole exons" "have been" excluded"
"additional diversity" was generated" within 2 of the exons"
"additional diversity" utilized" "internal splice donor sites"
"additional diversity" utilized" "acceptor sites"

A variation in the cytoplasmic domain was shown to result from the alternative splicing of 2 exons.

"cytoplasmic domain variation" " results" "the alternative splicing of 2 exons"

Thus the genomic structure of CD44 is remarkably complex, and alternative splicing is the basis of its structural and functional diversity.

"the genomic structure of CD44" "is" "remarkably complex,"
"alternative splicing" "is the basis of" "its structural diversity"
"alternative splicing" "is the basis of" "its functional diversity"

Splice variants of the glycoprotein CD44 may be associated with metastases and therefore may be useful in the early detection of metastatic potential in surgical biopsy specimens, as well as in the early diagnosis of cancer in screening programs, assessment of remaining disease, and early detection of recurrence (Matsumura and Tarin, 1992).

"glycoprotein CD44 splice variants" "may be associated with" "metastases"
"glycoprotein CD44 splice variants" "may be useful in" "the early detection of metastatic potential in surgical biopsy specimens"
"glycoprotein CD44 splice variants" "may be useful in" "the early diagnosis of cancer in screening program"
"glycoprotein CD44 splice variants" "may be useful in" "assessment of remaining disease"
"glycoprotein CD44 splice variants" "may be useful in" "early detection of recurrence"

Mayer et al. (1993) found that expression of CD44 expression which is not found in normal gastric mucosa and is found in only 49% of primary tumors, was associated with distant metastases at time of diagnosis and with tumor recurrence and increased mortality from gastric cancer.

Mayer et al. (1993) found that
" CD44" "is not found in" "normal gastric mucosa"
"CD44" "is found in" "only 49% of primary tumors"
"CD44" "was associated with" " distant metastases at time of diagnosis"
"CD44" "was associated with" "tumor recurrence"
"CD44" "was associated with" "increased mortality from gastric cancer"

Weber et al. (1996) noted that the CD44 gene encodes a transmembrane protein that is expressed as a family of molecular isoforms generated from alternative RNA splicing and posttranslational modifications.

Weber et al. (1996) noted that
" the CD44 gene" "encodes" "a transmembrane protein"
"The transmembrane protein" "is expressed" "as a family of molecular isoforms"
"the molecular isoforms" "are generated from" "alternative RNA splicing"
"the molecular isoforms" "are generated from" "posttranslational modifications"

Certain CD44 isoforms that regulate activation and migration of lymphocytes and macrophages may also enhance local growth and metastatic spread of tumor cells.

"Certain CD44 isoforms" "regulate" "activation of lymphocytes"
"Certain CD44 isoforms" "regulate" "migration of lymphocytes"
"Certain CD44 isoforms" "regulate" "migration of macrophages"
"Certain CD44 isoforms" "may enhance" "local growth"
"Certain CD44 isoforms" "may enhance" "metastatic spread of tumor cells"

One ligand of CD44 is hyaluronic acid, binding of which to the NH2-terminal domain of CD44 enhances cellular aggregation and tumor cell growth.

" hyaluronic acid" "is" "one ligand of CD44"
" hyaluronic acid "binds to" "the NH2-terminal domain of CD44"
"Binding" "enhances" "cellular aggregation"
"Binding" "enhances" "tumor cell growth"

(Krainer et al. (1991) referred to CD44 as a 'hyaladherin' -- see 601269.) Weber et al. (1996) demonstrated that another ligand is osteopontin (166490).

"(Krainer et al. (1991)" "referred to CD44 as" "a 'hyaladherin' -- see 601269.)"
" Weber et al. (1996)" "demonstrated that another ligand is" "osteopontin (166490)."

Osteopontin induces cellular chemotaxis but not homotypic aggregation of cells, whereas the inverse is true for the interaction between CD44 and hyaluronate.

"Osteopontin" "induces" "cellular chemotaxis"
"Osteopontin" "does not induce" "homotypic aggregation of cells"
"the inverse" "is true for" "the interaction between CD44 and hyaluronate"

The alternative responses to CD44 ligation may be exploited by tumor cells to allow OPN-mediated metastatic spread and hyaluronate-dependent growth in newly colonized tissues in the process of tumor metastasis.

"CD44 ligation alternative responses" "may be exploited by" "tumor cells"
"Explotation" "may allow" "OPN-mediated metastatic spread"
"Explotation" "may allow" "hyaluronate-dependent growth in newly colonized tissues in the process of tumor metastasis"

A table of all the CD antigens was provided by Schlossman et al. (1994) with a list of the common names, the size in kilodaltons, and the nature of the protein (adhesion, myeloid, platelet, and B cell, T cell, etc.).

" Schlossman et al. (1994" "provided" "A table of all the CD antigens"
"The CD antigen table" "contained" "a list of the common names"
"The CD antigen table" "contained" "the size in kilodaltons"
"The CD antigen table" "contained" "the nature of the protein"
"The CD antigen table" "contained" "the nature of adhesion
"The CD antigen table" "contained" "the nature of myeloid
"The CD antigen table" "contained" "the nature of platelet"
"The CD antigen table" "contained" "the nature of B cell"
"The CD antigen table" "contained" "the nature of T cell, etc."

Sherman et al. (1998) investigated the role of CD44 proteins in early limb development.

"Sherman et al. (1998" ") investigated" "the role of CD44 proteins in early limb development"

Members of this family of transmembrane glycoproteins are expressed by cells of the limb bud, including those of the apical ectodermal ridge (AER)

"Members of this transmembrane glycoprotein family" "are expressed by" "cells of the limb bud"
"cells of the limb bud" "include" "those of the apical ectodermal ridge (AER)"

Distinct CD44 variants are generated from a single gene by alternative RNA splicing of up to 10 variant exons and by extensive posttranslational modifications.

"Distinct CD44 variants" "are generated from"" a single gene"
"Distinct CD44 variants" "are generated by" "alternative RNA splicing of up to 10 variant exons"
"Distinct CD44 variants" "are generated" "by extensive posttranslational modifications"

The amino acid sequences encoded by these variant exons are located in the extracellular portion of the protein near the transmembrane domain.

" amino acid sequences" "are encoded by" "these variant exons"
"these variant exons" "are located in" "the extracellular portion of the protein"
"the extracellular portion of the protein" "is" "near the transmembrane domain"

A standard form of CD44 lacking these variant sequences is expressed by numerous cell types and is the smallest CD44 protein.

"A standard form of CD44"lacks" "these variant sequences"
"This form" "is expressed by" "numerous cell types"
"This form" "is" "the smallest CD44 protein"

It carries no variant exon sequences.

"It" "carries" "no variant exon sequences"

Splice variants are expressed in only a limited number of tissues and in certain tumors.

"Splice variants" "are expressed in" "only a limited number of tissues"
"Splice variants" "are expressed in" "only in certain tumors"

Signals from the AER of the developing vertebrate limb, including fibroblast growth factor-8 (600483), can maintain limb mesenchymal cells in proliferative state.

"the AER of the developing vertebrate limb" "sends" signals"
"The signals" "includes fibroblast growth factor-8 (600483)"
"The signals" "can maintain" "limb mesenchymal cells in proliferative state"

Sherman et al. (1998) reported that a specific CD44 splice variant is crucial for the proliferation of these mesenchymal cells.

Sherman et al. (1998) reported that
" A specific CD44 splice variant" "is crucial for" "the proliferation of these mesenchymal cells"

Epitopes carried by this variant colocalize temporally and spatially with FGF8 in the AER throughout early limb development.

"this variant carries epitopes"
"Epitopes" "colocalize temporally"
"Epitopes" "colocalize" "spatially"
"Epitopes" "colocalize with" "FGF8 in the AER"
"Epitopes" "colocalize throughout" "early limb development"

A splice variant containing the same sequence expressed on model cells binds both FGF4 (164980) and FGF8 and stimulates mesenchymal cells in vitro.

"A splice variant" "contains" "the same sequence expressed on model cells"
"A splice variant" "binds" "FGF4 (164980)"
"A splice variant" "binds" "FGF8"
"A splice variant" "stimulates" "mesenchymal cells in vitro"

Sherman et al. (1998) found that when applied to the AER, an antibody against a specific CD44 epitope blocked FGF presentation and inhibited limb outgrowth.

Sherman et al. (1998) found that when applied to the AER,
" an antibody against a specific CD44 epitope" "blocked" "FGF presentation"
" an antibody against a specific CD44 epitope" "inhibited limb outgrowth"

Therefore, CD44 is necessary for limb development and functions in a novel growth factor presentation mechanism likely relevant to other physiologic and pathologic situations in which a cell surface protein presents a signaling molecule to a neighboring cell.

"CD44" "is necessary for" "limb development"
"CD44" "functions in" "a novel growth factor presentation mechanism"
"CD44" "is likely relevant to" "other physiologic situations when a cell surface protein presents a signaling molecule to a neighboring cell"
"CD44" "is likely relevant to" "other pathologic situations when a cell surface protein presents a signaling molecule to a neighboring cell"