Protein kinase patterns in hyperplastic rat thyroids and in human non-toxic nodular goitres

Toru-Delbauffe, D.; Ohayon, Renée; Pavlović-Hournac, M.

doi:10.1016/0303-7207(83)90172-7

Cited by 4 publications

(3 citation statements)

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“…It was suggested that phosphorylation of proteins is impor tant in determining the biological properties of tumor cells [2], In these studies, in which endogenous phosphorylation assays were performed, no attempt was made to distin guish between cAMP-dependent and -inde pendent protein kinases [1,2], Nakaya et al [3], however, showed that the protein ki nases, selectively phosphorylating three cy tosolic proteins in AH-66 hepatoma ascites cells, but absent from normal liver, belonged to the group of (cAMP-independent) casein kinases. In contrast, in rat hyperplastic thy roid glands [4], greater increases in the con tent of cAMP-dependent protein kinases were observed than in casein kinases, al though these activities were characterized using exogenous substrates.…”

Section: Introductionmentioning

confidence: 97%

“…cAMPdependent protein kinase activity, investi gated using exogenous substrate, has pre viously been detected in various cancerous cells, e.g. differentiating HL60 cells [31], rat liver during hepatocarcinogenesis [32], hu man glioblastoma and other intracranial ma lignancies [33,34], rat prostate and Dunning prostatic tumors [35], hyperplastic rat thy roid glands and human nontoxic nodular goiters [4]. However, it is noteworthy that Kasai and Field [24] were not able to demon strate cAMP-dependent protein kinase activ ity using endogenous protein as substrate, although it was detected using exogenous histones as substrate.…”

Section: General Findingsmentioning

confidence: 99%

“…Cyclic nucleo tide-independent protein kinase activities can also be measured using exogenous sub strates and have been detected in many tu morous and nontumorous tissues [3,4,24,31,36]. They appear to exert important reg ulatory functions since quantitative changes in their expression have been described to occur during induction of differentiation [31], either promotion or suppression of preneoplastic carcinogenic foci [37] and in volution of hyperplastic thyroid glands [4], The appearance of alterations in the content of (cyclic nucleotide-independent) protein kinases following the dedifferentiation pro cess may therefore be a plausible explanation for the different phosphorylation intensities between DMTCs and AMTCs.…”

Section: General Findingsmentioning

confidence: 99%

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Protein Phosphorylation and Tyrosine Kinase Activity in Medullary Thyroid Carcinomas of the Rat

Oskam

Meerendonk²,

Boer³

et al. 1987

Tumor Biol

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The kinetics of endogenous protein phosphorylation and resultant phosphopro-tein patterns were investigated in well-differentiated (DMTC) and undifferentiated (AMTC) medullary thyroid carcinomas of the rat. Cytosolic or particulate fractions from these tumors were incubated with γ-32P-ATP in the presence of various effectors. Phosphorylation appeared to be predominantly independent of exogenously added cyclic AMP. Magnesium and manganese were equally effective cofactors. For both tumor types ³²P incorporation into cytosolic proteins was maximal within 3–4 min after addition of ATP and subsequently decreased gradually within 1 h. In contrast, in particulate preparations maximal incorporation was reached within 30 s and remained constant over a relatively long time span. In both cases, however, ³²P incorporation in extracts from DMTCs were 50–100% higher as compared to AMTCs. Comparison of the phosphoprotein patterns of each tumor after in vitro phosphorylation showed some significant differences. A phosphoprotein with molecular weight of 90 kilodalton (90 kD) was exclusively expressed in the cytosol of DMTC, whereas 99- and 84-kD phosphoproteins were only present in the cytosol of AMTC. The DMTC particulate fraction contained two phosphoproteins (with molecular weights of 40 and 37 kD), which were absent from that of AMTC. In addition, a number of proteins were more intensely phosphorylated in one of the tumors, e.g. proteins of 94 and 33 kD in DMTC cytosol and a protein of 78 kD in AMTC cytosol. Calcium induced phosphorylation of five proteins in DMTC cytosol (with molecular weights of 69, 55, 49, 43 and 32 kD), which were less intensely or not phosphorylated in AMTC. Tyrosine kinase activity was investigated using exogenously added poly(glutamine:tyrosine, 4:1) as an artificial substrate. Cytosolic tyrosine kinase activity in DMTC was ± 50% higher than in AMTC (11.9 ± 0.6 and 8.2 ± 1.7 pmol/mg/min, respectively). The enzyme activities in the paniculate preparations were much higher than in the cytosols ( ± 100 pmol/mg/min), although considerable variations in enzyme activity between different tumors of either type were observed. Quantitative differences in tyrosine kinase activity between AMTC and DMTC particulate fractions did not seem to exist using this substrate. Phosphoamino acid analysis of endogenously phosphorylated proteins in both AMTC and DMTC showed phosphotyrosine to be present only in cytosolic proteins within the 50-kD molecular weight region, the majority of ³²P being on serine and some on threonine. Thus, this study shows that significant differences in protein phosphorylation and tyrosine kinase activity exist between these well-differentiated and undifferentiated carcinomas.

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Section: Introductionmentioning

confidence: 97%

Section: General Findingsmentioning

confidence: 99%