RHAMM

A vertebrate homologue of the cell cycle control protein CDC37 was recently cloned and found to be an hyaladherin,62 as was a protein that copurified with the splicing factor SF2.63 An intracellular form of the HA receptor RHAMM was demonstrated to regulate erk kinase activity. Changes in function of these intracellular, depending on whether or not they have HA molecules attached, confers another layer of complexity dependent on intracellular hyaluronidase enzymes. 

The other major receptor for HA is receptor for HA-mediated motility (RHAMM),133,134 discovered and characterized by Eva Turley. This receptor is implicated in cell locomotion, focal adhesion turnover, and contact inhibition. It also is expressed in a number of variant isoforms. The interactions between HA and RHAMM regulate locomotion of cells by a complex network of signal transduction events and interaction with the cytoskeleton of cells. It is also an important regulator of cell growth.135... 

The TGF-/3 stimulation of fibroblast locomotion utilizes RHAMM. TGF-/3 is a potent stimulator of motility in a wide variety of cells. In fibroblasts, TGF-/3 triggers the transcription, synthesis, and membrane expression of not only RHAMM, but also the synthesis and expression of the HA, all of which occurs coincident with the initiation of locomotion.136... 

The hyaluronasome, because of its ability to respond to extracellular events as well as to the intracellular metabolic state of the cell may contain HA receptors such as RHAMM and CD44, HA synthase enzymes, the hyaluronidases, hyaluronidase inhibitors,247,248 the /i-cxoglycosidascs, and HA-binding proteins such as HABP1.249... 

Mohapatra, S. et al., Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression, J. Exp. Med., 183, 1663, 1996. 

Samuel, S.K. et al., TGF-beta 1 stimulation of cell locomotion utilizes the hyaluronan receptor RHAMM and hyaluronan,./. Cell Biol., 123, 749, 1993. 

Hofmann, M. et al., Problems with RHAMM a new link between surface adhesion and oncogenesis Cell, 95, 591, 1998. 

NStA Wolfenbilttel, 1 Alt 9, Nr. 306, fols. 99-93. Hoping to put these rumors to rest, Julius wrote to Philipp s former patron, Duke Johann Friedrich of Sachsen-Gotha, and asked him to vouch for Philipp s character, which the Saxon duke gladly did. See Rhamm, Die betriiglichen Goldmacher, 21 and NStA Wolfenbilttel, 1 Alt 9, Nr. 307, fols. 169-70. 

Kraschewski, Wirtschaftspolitik, 730-37. For more on Rhenanus, see Moran, The Alchemical World of the German Court, 76 Rhamm, Die betriiglichen... 

Rhamm, Albert. Die betriiglichen Goldmacher am Hofe des Herzogs fulius von Braunschweig Nach den Processakten. Wolfenbiittel Julius Zwifiler, 1883. 

De novo synthesized HA may be secreted from the cell and subsequently interact with different cell surface receptors, such as CD44, the receptor for HA-mediated motility (RHAMM), the HA receptor for endocytosis (HARE) and many others. It has become evident that these processes mediate at least three different, very important physiological processes signal transduction, formation of pericellular coats, and the receptor-mediated internalization. 

RHAMM is a HA receptor that can be present either on the cell surface, in the cytoplasm or even in the nucleus. Interactions between RHAMM and HA may trigger a lot of cellular signaling pathways, including those that involve protein kinase C, MAP kinases, phosphatidylinositol and tyrosine kinases [125]. Several recent studies have clearly demonstrated the involvement of RHAMM in the locomotion of TGF-)9-stimulated fibroblasts, smooth muscle cells, macrophages as well as Ras-transformed fibroblasts [126], i.e. the processes that are most likely important in the development of cancer. 

Metastasis Hyaluronate receptor CD44 and RHAMM Galectins E Selectins 140] [132]... 

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