STIMULATION OF RECEPTOR-ASSOCIATED KINASE, TYROSINE KINASE, AND MAP KINASE IS REQUIRED FOR PROLACTIN-MEDIATED MACROMOLECULAR BIOSYNTHESIS AND MITOGENESIS IN NB2 LYMPHOMA

Citation
Gb. Carey et Jp. Liberti, STIMULATION OF RECEPTOR-ASSOCIATED KINASE, TYROSINE KINASE, AND MAP KINASE IS REQUIRED FOR PROLACTIN-MEDIATED MACROMOLECULAR BIOSYNTHESIS AND MITOGENESIS IN NB2 LYMPHOMA, Archives of biochemistry and biophysics, 316(1), 1995, pp. 179-189
Citations number
39
Categorie Soggetti
Biology,Biophysics
ISSN journal
00039861
Volume
316
Issue
1
Year of publication
1995
Pages
179 - 189
Database
ISI
SICI code
0003-9861(1995)316:1<179:SORKTK>2.0.ZU;2-S
Abstract
Lactogens [prolactin (Prl) and growth hormone] stimulate phosphorylati on of the 40S ribosomal protein, S6, in Nb2 cells by mechanisms that d o not involve participation of cAMP or protein kinase A, protein kinas e C, or cGMP-dependent protein kinase. However, inhibition of tyrosine kinase (TK) abrogates Prl-mediated macromolecular biosynthesis. Inasm uch as lactogen signaling may involve sequential activation of protein kinases, the effect of Prl on the well-characterized mitogen-activate d protein kinase (MAPK) and S6 kinase (S6K), the enzyme responsible fo r S6 phosphorylation in vivo, and their relationship to Nb2 macromolec ular biosynthesis and mitogenesis were investigated. The results show that MAPK stimulation is transient (peak activity, 30 min) and precede s that of S6K, which reaches a maximum at 1.5-2 h, and slowly returns towards control levels at 6 h. Both staurosporine which inhibits GH re ceptor-associated kinase (JAK2) and genistein (GEN), an inhibitor of m embrane-associated and cytoplasmic TRs, abrogate Prl-stimulated TK, MA PK, and S6K. Rapamycin (RAP), a specific inhibitor of p70(S6K), comple tely blocks S6K but does not affect TK and MAPK. TR and MAPK activity correlates with Prl-stimulated anabolism, i.e., protein and DNA synthe sis and mitogenesis. Thus, concentrations of STR and GEN which abrogat e TK and MAPK inhibit anabolism virtually 100%. However, RAP, which in hibits S6K (ca. 100%) but not TK or MAPK, only delays Prl-mediated ana bolism. These results indicate that Prl signaling in Nb2 cells involve s a protein kinase cascade and that regulation of receptor-associated kinase, TK, and MAPK correlates with anabolism, The role of S6K (and S 6 phosphorylation) appears to be ancillary. (C) 1995 Academic Press, I nc.