ALPHA-MELANOCYTE-STIMULATING HORMONE AND ENDOTHELIN-1 HAVE OPPOSING EFFECTS ON MELANOCYTE ADHESION, MIGRATION, AND PP125(FAK) PHOSPHORYLATION

Recent reports show that alpha-MSH (melanocyte-stimulating hormone) is mitogenic and melanogenic for normal human melanocytes, and that this effect is mediated through binding to the melanocortin receptor (MC1R ) and activation of cAMP formation. alpha-MSH has also been shown to i nduce changes in cell shape in melanocytes and melanoma cells, particu larly increased dendricity, suggesting a potential role for alpha-MSH in melanocyte-matrix interactions and pigment transfer through reorgan ization of the melanocyte actin filament cytoskeleton. In this report we show that the potent alpha-MSH analog (Nle(4), D-Phe(7))-alpha-MSH (NDP-MSH) induces reorganization of the actin stress fiber cytoskeleto n in treated human melanocytes and that this reorganization is associa ted with increased adhesion to fibronectin (FN), Because most melanocy te growth factors act synergistically on melanocyte mito genesis, we a lso sought to determine the effect of the melanocyte mitogen endotheli n-1 (ET-I) on the melanocyte actin cytoskeleton, melanocyte adhesion, and melanocyte migration. We show that ET-1, which increases melanocyt e migration on FN, has opposite effects on melanocyte adhesion to FN c ompared with NDP-MSH and that endothelin-1-induced actin reorganizatio n is distinct from that observed following NDP-MSH treatment. Finally, we show that focal adhesion kinase (pp125(FAR)), a nonreceptor tyrosi ne kinase associated with focal contact formation and cell migration, is phosphorylated on tyrosine residues after treatment of melanocytes with ET-1, but not NDP-MSH. These data indicate that while alpha-MSH a nd ET-I act synergistically to modulate melanocyte proliferation, they have opposite effects on melanocyte-matrix interactions. (C) 1997 Aca demic Press.