ANTAGONISM OF CONCANAVALIN-A CAPPING IN PHORBOL ESTER-ACTIVATED LYMPHOCYTES BY CALMODULIN INHIBITORS AND CERTAIN AMINO-ACID ESTERS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (6) , 2115-2120
Abstract
12-O-Tetradecanoylphorbol-13-acetate (TPA), an effective tumor promoter in mouse skin and comitogen in bovine lymphocytes, rapidly stimulates concanavalin-A-mediated cap formation in the latter cells. The ability of different phorbol derivatives to facilitate the capping reaction correlates well with their potencies as lymphocyte comitogens and as tumor-promoting agents. This effect of TPA on capping in bovine lymphocytes, which is apparent within minutes is neither mimicked nor altered by dibutyryl cAMP or cGMP. Cytochalasin D, a microfilament-disrupting agent, inhibits cap formation, thereby suggesting the participation of microfilaments in the response. Benzoyl tyrosine ethyl ester selectively inhibits the TPA-stimulated cap formation, whereas benzoyl tyrosinamide is inactive. A comparison of related amino acid derivatives reveals that their activities are dependent on the nature of both the amino acid side chain and the carboxyl end blocking group . Trifluoperazine and N-(6-aminohexyl)-5-chloronaphthalenesulfonamide, known inhibitors of the calmodulin-dependent processes, also selectively block the TPA-stimulated cap formation, whereas trifluoperazine sulfoxide, a less effective calmodulin antagonist, is relatively inactive. The stimulation of capping by TPA apparently involves the activation of a calmodulin-dependent process which may also be regulated by the function of an esterase.