| Popis: |
Signal transduction by CD44 has been associated with the activation of signaling molecules that support cell growth, including members of the Ras family of small GTP-binding proteins; an intracellular membraneassociated tyrosine kinase, focal adhesion kinase (FAK); phosphtidylinositol 3-kinase (PI3K) and its downstream target, the Akt kinase; the cytoplasmic serine/threonine kinase, p42/p44 mitogen-activated protein kinase (MAPK); and members of the src family of cytoplasmic tyrosine kinases. These proteins have been independently shown to support cell growth and survival in many cell types. The pathways activated by CD44, and the mechanism of activation, appear to depend on both the cell type examined and the splice variant of CD44 that is expressed. Further, PH-20 acts as both a hyaluronidase and an HA receptor, and signaltransduction downstream of PH-20 activation has mostly been reported in relation to sperm maturation and function. In addition, the discovery of RHAMM as a key regulator of cellular migration and proliferation led to the hypothesis that RHAMM could also function downstream of receptor kinase signaling. A number of studies with transformed cell lines indicate that RHAMM is required for H-Ras and serum downstream activation of p42/p44 MAPK. The ability of PDGF to signal through its tyrosine kinase receptor and activate p42/p44 MAPK, as well as other phosphoproteins, depended upon the level of RHAMM expression on the surface of 10T1/2 murine fibroblasts. |
