摘要:

AbstractThe effect of the skin tumor‐promoter TPA (12‐O‐tetradecanoylphorbol‐13‐ace‐tate) on expression of cellular proto‐oncogenes has been examined in cell lines derived from human urothelium. A single treatment with TPA (1 μg/ml) increased the transcription of c‐fosand c‐mycproto‐oncogenes at least 20‐fold in the mortal cell line HU 1752. The induction was transient and was accompanied by a rapid but transient change in cell morphology. When immortalized cell lines were treated with TPA a similar rapid and transient morphological response was observed, but the TPA treatment only increased the level of c‐fosmRNA. suggesting that the normal regulation of c‐myctranscription is altered in immortalized cells irrespective of their tumorigenic properties. The levels of c‐Ha‐rasand c‐Ki‐rasmRNAs were unaffected

ISSN:0730-2312    

DOI:10.1002/jcb.240340202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractDegradation of intracellular proteins via the ubiquitin pathway involves several steps. In the initial event, ubiquitin becomes covalently linked to the protein substrate in an ATP‐requiring reaction. Following ubiquitin conjugation, the protein moiety of the adduct is selectively degraded with the release of free and reusable ubiquitin. Ubiquitin modification of a variety of protein targets in the cell plays a role in basic cellular functions. Modification of core nucleosomal histones is probably involved in regulation of gene expression at the level of chromatin structure. Ubiquitin attachment to cell surface proteins may play roles in processes of cell‐cell interaction and adhesion, and conjugation of ubiquitin to other yet to be identified protein(s) could be involved in the progression of cells through the cell cycle. Despite the considerable progress that has been made in the elucidation of the mode of action and cellular roles of the ubiquitin pathway, many major problems remain unsolved. A problem f central importance is the specificity in the ubiquitin ligation system. Why are certain proteins conjugated and committed for degradation, whereas other proteins are not? A free α‐NH2group is an important feature of the protein structure recognized by the ubiquitin conjugation system, and tRNA is required for the conjugation of ubiquitin to selective proteo‐lytic substrates and for their subsequent degradation. These findings can shed light on some of the features of a substrate that render it susceptile to ubiquitin‐mediated d

ISSN:0730-2312    

DOI:10.1002/jcb.240340203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractDuring ovulation, enzymatic degradation of the extracellular matrix occurs within and around the graafian follicles. In this study, the activities of several different proteolytic enzymes were measured in the culture media of follicles taken from pregnant mare serum gonadotropin (PMSG)‐primed immature rats. At 52 h after PMSG, the follicles were cultured for 2 to 15 h in media with or without human chorionic gonadotropin (hCG). Type I collagenase activity in hCG‐stimulated follicles gradually increased within 6 h to 3.3‐fold above that of the controls. Relatively pure populations of granulosa cells produced type I collagenase to a similar extent. Likewise, type IV collagenase increased 3.8‐fold by 6 h after exposure of the follicles to hCG. In contrast, plasminogen activator activity increased by 3.9‐fold at 2 h after hCG, but was negligible at 4, 6, and 15 h after incubation. These results suggest that plasminogen activator may activate both type I and type IV collagenase in hCG‐stimulated ovulator

ISSN:0730-2312    

DOI:10.1002/jcb.240340204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe cytoskeletal protein actin exists in vertebrates as six different isoforms, which are difficult to identify conclusively because of a high degree (>90%) of overall sequence homology. We have used IEF immunoblotting in combination with a panel of isoform‐specific and ‐selective antibodies to analyze the actin isoform composition of nine tissues from adult rat. In three nonmuscle tissues (lung, spleen, and testis), we detected a previously unreported isoform that we identified as smooth muscle α. The IEF immunoblot technique was also used to quantify the proportions of the isoforms expressed in these nine rat tis

ISSN:0730-2312    

DOI:10.1002/jcb.240340205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractVanadate can activate the uptake of Ca in A431 epidermal carcinoma cells by two‐to fivefold with no detectable lag period. Preincubation with epidermal growth factor (EGF) to down‐regulate the EGF receptor prevents subsequent stimulation by EGF but not that by vanadate. Ca uptake is sodium‐independent and is not activated by depolarization in high KCl. On the contrary, vanadate‐stimulated uptake is completely inhibited by decreasing the plasma membrane potential from about −65 to −30 mV. These results demonstrate that the EGF receptor is not itself functioning as a Ca channel, that vanadate is not acting at the level of EGF receptor, and that the Ca transport system exhibits an unusual potential sensitivity in that it is inhibited by depolarization of the plas

ISSN:0730-2312    

DOI:10.1002/jcb.240340206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractTumor‐promoting phorbol esters, like growth factors, elicit pleiotropic responses involving biochemical pathways that lead to different biological responses. Genetic variant cell lines that are resistant to mitogenic, differentiation, or transformation responses to tumor promoters have been valuable tools for understanding the molecular bases of these responses. Studies using the mouse epidermal JB6 cell lines that are sensitive or resistant to tumor promoter‐induced transformation have yielded new understanding of genetic and signal transduction events involved in neoplastic transformation. The isolation and characterization of cloned mouse promotion sensitivity genespro‐1 andpro‐2 is reviewed. A new activity ofpro‐1 has been identified: when transfected into human cancer prone basal cell nevus syndrome fibroblasts but not normal fibroblasts mousepro‐1 confers lifespan extension on these cells. Recently, we have found that apro‐1 homolog from a library of nasopharyngeal carcinoma, but not the homolog from a normal human library, is activated for transferring promotion sensitivity. The many genetic variants for responses to tumor promoters have also proved valuable for signal transduction studies. JB6 P‐ cells fail to show the 12‐O‐tetradecanoyl‐phorbol‐13‐acctate (TPA)‐induced synthesis of two proteins of 15 and 16 kD seen in P+cells. P−, P+, and TPA transformed cells show a progressive decrease in both basal and TPA‐inducible levels of a protein kinase C substrate of 80 kD. P−cells are relatively resistant both to anchorage‐independent transformation and to a protein band shift induced by The calcium analog lanthanum. It appears that one or more calcium‐binding proteins and one or moreprogenes may be critical determinants of tumor promo

ISSN:0730-2312    

DOI:10.1002/jcb.240340207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractPlatelet‐derived growth factor (PDGF) increases the mitogenic activity of epidermal growth factor (EGF) in several cells lines, including BALB/C‐3T3. PDGF‐treated BALB/C‐3T3 cells manifest a reduced capacity to bind125I‐labeled EGF due to a loss of high affinity EGF receptors. Cholera toxin potentiates the ability of PDGF to both decrease EGF binding and initiate mitogenesis. Whether PDGF increases EGF sensitivity via its effects on EGF receptors is not known and requires a more complete understanding of the mechanism by which PDGF decreases EGF binding.12‐0‐tetradecanoylphorbol 13‐acetate (TPA) also reduces EGF binding in BALB/C‐3T3 and other cells, presumably by activating protein kinase C and, consequently, inducing the phosphorylation of EGF receptors at threonine–654. PDGF indirectly activates protein kinase C, and EGF receptors in PDGF‐treated WI‐38 cells are phosphorylated at threonine‐654. Thus, the effects of PDGF on EGF binding may also be mediated by protein kinase C. We investigated this hypothesis by comparing the actions of PDGF and TPA on EGF binding in density‐arrested BALB/C‐3T3 cells.Both PDGF and TPA caused a rapid, transient, cycloheximide‐independent loss of251‐EGF binding capacity. The actions of both agents were potentiated by cholera toxin. However, whereas TPA allowed EGF binding to recover, PDGF induced a secondary and cycloheximide‐dependent loss of binding capacity. Most importantly, PDGF effectively reduced binding in cells refractory to TPA and devoid of detectable protein kinase C activity. These findings indicate that PDGF decreases EGF binding by a mechanism that involves protein synthes

ISSN:0730-2312    

DOI:10.1002/jcb.240340208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

ISSN:0730-2312    

DOI:10.1002/jcb.240340201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY