The Journal of Immunology, Vol 143, Issue 3 956-963, Copyright © 1989 by American Association of Immunologists

ARTICLES

Human peripheral lymphocyte growth regulation and response to phorbol esters is linked to synthesis and phosphorylation of the cytosolic protein, prosolin

HL Cooper, E McDuffie and R Braverman
Cell and Molecular Physiology Section, National Cancer Institute, Bethesda, MD 20892.

Prosolin is a major cytosolic protein (Mr 18400, isoelectric point 5.9) first reported in HL-60 promyelocytic leukemia cells. It is rapidly phosphorylated (15 to 30 min) in response to TPA treatment as an early event in a sequence that leads to cessation of cell proliferation and to differentiation of promyelocytes into monocytes. In our study we examined the expression of prosolin in human peripheral lymphocytes and investigated the effects of TPA treatment on prosolin phosphorylation and on lymphocyte proliferation. Prosolin was not expressed in resting PBL but was induced after 24 to 36 h of PHA stimulation, simultaneously with induction of DNA synthesis. In rapidly proliferating (IL-2 dependent) PBL prosolin was a major cytosolic component, comprising 0.5% of total cytosolic protein, of which approximately 28% was phosphorylated. Expression of prosolin decreased again when either mitogen-induced or IL-2-dependent proliferation diminished during extended periods in culture. Thus, expression of prosolin is correlated with periods when PBL are cycling through S-phase. TPA treatment of IL- 2-dependent PBL at the peak of their growth caused phosphorylation of about two-thirds of preexisting unphosphorylated prosolin within 1 h. This was accompanied by cessation of cell proliferation, as indicated by measurements of TdR incorporation. Although TPA has well known mitogenic effects in lymphocytes during initial activation, this result shows that it exerts an antiproliferative effect in rapidly dividing PBL. It is suggested that increased phosphorylation of prosolin may be an initiating event in the antiproliferative response to TPA, which would occur only in proliferating lymphocytes expressing prosolin.

This article has been cited by other articles:

				W. Liedtke, E. E. Leman, R. E. W. Fyffe, C. S. Raine, and U. K. Schubart Stathmin-Deficient Mice Develop an Age-Dependent Axonopathy of the Central and Peripheral Nervous Systems Am. J. Pathol., February 1, 2002; 160(2): 469 - 480. [Abstract] [Full Text] [PDF]

				S. le Gouvello, V. Manceau, and A. Sobel Serine 16 of Stathmin as a Cytosolic Target for Ca2+/Calmodulin-Dependent Kinase II After CD2 Triggering of Human T Lymphocytes J. Immunol., August 1, 1998; 161(3): 1113 - 1122. [Abstract] [Full Text] [PDF]

				S. V. Drouva, B. Poulin, V. Manceau, and A. Sobel Luteinizing Hormone-Releasing Hormone-Signal Transduction and Stathmin Phosphorylation in the Gonadotrope {alpha}T3-1 Cell Line Endocrinology, May 1, 1998; 139(5): 2235 - 2239. [Abstract] [Full Text] [PDF]

				S. B. Horwitz, H.-J. Shen, L. He, P. Dittmar, R. Neef, J. Chen, and U. K. Schubart The Microtubule-destabilizing Activity of Metablastin (p19) Is Controlled by Phosphorylation J. Biol. Chem., March 28, 1997; 272(13): 8129 - 8132. [Abstract] [Full Text] [PDF]

				U. K. Schubart, J. Yu, J. A. Amat, Z.-q. Wang, M. K. Hoffmann, and W. Edelmann Normal Development of Mice Lacking Metablastin (P19), a Phosphoprotein Implicated in Cell Cycle Regulation J. Biol. Chem., June 14, 1996; 271(24): 14062 - 14066. [Abstract] [Full Text] [PDF]