Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

Figure 4

Model of RHAMM signaling. Model summarizes the known signaling functions of cell surface and intracellular RHAMM. Cell surface RHAMM interacts with CD44, HA, and growth factors to activate protein tyrosine kinase signaling cascades that activate the ERK1,2 MAP kinase cascade. This signaling can increase random motility in the absence of intracellular RHAMM. Intracellular RHAMM also binds to a number of protein partners that mediate its functions as a regulator of microtubule dynamics, centrosome structure/function, and gene expression. For example, during interphase, cytoplasmic RHAMM:protein partner interactions (MEK1/ERK1,2 shown) contribute to the dynamic properties of interphase microtubules and the number, placement, and structure of centrosomes, which affect cell polarity and direct cell migration. Nuclear RHAMM:MEK1:ERK1,2 complexes also control expression of genes involved in cell motility such as PAI-1 and MMP-9. During the cell cycle, RHAMM:TPX2 complexes contribute to mitotic spindle integrity and cell cycle progression through G2M while RHAMM:supervillin complexes promote cytokinesis.