Membrane-bound protein kinase C modulates receptor affinity and chemotactic responsiveness of Lewis lung carcinoma sublines to an elastin-derived peptide.
The M27 and H59 variants of Lewis lung carcinoma differ in their responsiveness to the chemotactic elastin peptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG). M27 cells, selected for metastasis to lung, are highly responsive to a positive gradient of VGVAPG. H59 cells, selected for metastasis to liver, do not migrate in response to VGVAPG. Although both cell types bind radiolabeled VGVAPG, Scatchard analysis of 125I-Tyr-VGVAPG binding reveals that M27 cells bind the chemoattractant with a Kd of 2.7 nM, whereas nonresponsive H59 cells bind the peptide with a Kd of 67 nM. These findings indicate that the failure of H59 cells to migrate in response to VGVAPG may be due to the reduced affinity of their VGVAPG receptors. Both receptor affinity and chemotactic responsiveness to VGVAPG can be modulated in each of these two tumor cell lines by the levels of active membrane-associated protein kinase C. Treatment of nonresponsive H59 cells with 12-O-tetradecanoylphorbol 13-acetate increases the level of membrane-bound protein kinase C activity with a concomitant increase in VGVAPG binding affinity and induction of chemotactic responsiveness to VGVAPG. Treatment of M27 cells with the protein kinase C inhibitor, staurosporine, reduces VGVAPG binding affinity and abrogates the chemotactic response. We conclude that chemotactic responsiveness of M27 and H59 tumor cells is dependent upon high VGVAPG receptor affinity, which is strongly correlated to high levels of membrane-bound protein kinase C activity.
Blood
C H
CH
Department of Cellular and Molecular Physiology, Children's Hospital, Boston, Massachusetts.
Zetter
B R
BR
D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D007700:Kinetics; D008175:Lung Neoplasms / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D009842:Oligopeptides; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate