• CD44v
• CD44v9

MAJOR LINKS FOR CD44R  

• No information

• The activity of the many isoforms of CD44R remains to be clarified
• The expression of variant isoforms of CD44 appear to correlate with HA-binding, but this is not yet clear

CELLULAR FUNCTION OF CD44R  

• CD44R, and in particular CD44v6-containing isoforms, may be involved in leukocyte attachment to and rolling on endothelial cells, homing to peripheral lymphoid organs and to sites of inflammation

DISEASE RELEVANCE OF CD44R AND FUNCTION OF CD44R IN INTACT ANIMAL  

• Expression of CD44v6 in a non-metastatic rat pancreatic adenocarcinoma conferred metastatic potential, and mAbs to CD44v6 inhibited metastasis, suggesting a role for CD44v6-containing isoforms in tumor metastasis

MOLECULAR STRUCTURE OF CD44R  

• CD44R isoforms contain almost all of the 341 amino acids of the standard form of CD44 with insertion of a variable number of amino acids, encoded by exons 6-14 in humans, in the membrane proximal region of the extracellular domain
• At least 18 different alternatively spliced CD44 isoforms have been reported thus far
• CD44R isoforms have the same transmembrane and cytoplasmic domains as the standard form of CD44

MOLECULAR MASS OF CD44R  

POST-TRANSCRIPTIONAL MODIFICATION OF CD44R  

• CD44 exons 6-14 (v2-v10) in humans can be variably spliced into standard CD44 encoded by exons 1-5, 15-17, and 19 leading to the production of CD44 variant isoforms

POST-TRANSLATIONAL MODIFICATION OF CD44R  

• Insertion of a variable number of amino acids in the membrane-proximal region of the extracellular domain due to alternative splicing gives additional sites for N- and O-linked linked carbohydrate modification
• Exon 8 (variant exon 3)-containing CD44 isoforms can also be modified by heparan sulfate

SUBSTRATES FOR CD44R   - Unknown

ENZYMES WHICH MODIFY CD44R   - Protein kinase C

LIGANDS FOR CD44R AND MOLECULES ASSOCIATED WITH CD44R   - See CD44 CD guide

• CD44R represents a heterogeneous group of CD44 variant isoforms expressed constitutively in epithelial cells and monocyte lineage cells and can be upregulated in activated leukocytes

• Isoforms of CD44 containing inserts of variant exons may be referred to by the variant exons (1-10 for mouse and rat, and 2-10 for human) that they contain. For example, a CD44 isoform containing variant exon 6 may be referred to as CD44v6; an isoform containing CD44 variant exons 8, 9 and
• 10 may be referred to as CD44v8-10

SELECTION OF OTHER CD44R-SPECIFIC REFERENCE MAB   - 11.24 (CD44v9)

REVIEWS

1. Haynes BF,Liao HX,Patton KL The transmembrane hyaluronate receptor (CD44): multiple functions, multiple forms. Cancer Cells 1991 3:347 PubMed

2. Lesley J,Hyman R,Kincade PW CD44 and its interaction with extracellular matrix. Adv Immunol 1993 54:271 PubMed

PRIMARY CITATIONS

3. Bartolazzi A,Nocks A,Aruffo A,Spring F,Stamenkovic I Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. J Cell Biol 1996 132:1199 PubMed

4. Bennett KL,Jackson DG,Simon JC,Tanczos E,Peach R,Modrell B,Stamenkovic I,Plowman G,Aruffo A CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. J Cell Biol 1995 128:687 PubMed

5. Jackson DG,Bell JI,Dickinson R,Timans J,Shields J,Whittle N Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon. J Cell Biol 1995 128:673 PubMed

6. Levesque MC,Haynes BF In vitro culture of human peripheral blood monocytes induces hyaluronan binding and up-regulates monocyte variant CD44 isoform expression. J Immunol 1996 156:1557 PubMed

7. Liao HX,Levesque MC,Patton K,Bergamo B,Jones D,Moody MA,Telen MJ,Haynes BF Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies. J Immunol 1993 151:6490 PubMed

8. Mackay CR,Terpe HJ,Stauder R,Marston WL,Stark H,Gunthert U Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 1994 124:71 PubMed

9. Terpe HJ,Koopmann R,Imhof BA,Gunthert U Expression of integrins and CD44 isoforms in non-Hodgkin's lymphomas: CD44 variant isoforms are preferentially expressed in high-grade malignant lymphomas. J Pathol 1994 174:89 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov