An area of cytokine research that has received relatively little attention is the cytokine-induced cellular responses that are not directly related to mitosis. An example of a cytokine capable of inducing these types of cellular activities is TGF-beta. Earlier, we have shown that TGF-beta induces cellular hypertrophy in cultured, vascular, smooth muscle cells and, concomitantly, the stimulated cells exhibited an enhanced level of f- actin. This observation led to a series of studies on the cellular adhesion molecule, fibronectin, and its interactions with its receptor. With our collaborators, we have shown that 1) the receptor for the new cell-type specific binding domain of FN located within the alternatively spliced IIICS sequence, CS1, is alpha 4 beta 1 integrin complex, 2) the second cell binding domain located within the IIICS designated as CS5 has been shown also to bind to the same integrin alpha 4 beta 1 integrin complex, 3) VAL-4 mediates CD3-dependent CD4+ T cell activation via the CS1 peptide domain of fibronectin, and 4) the minimum essential amino acid sequence for the biological activity of CS1 peptide has been shown to be Leu-Asp-Val. Several recently established human melanoma cell lines are being screened for their CS1 dependency for cell spreading, and the functional role of the N-terminal CS1 peptide domain is being examined.
