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PubMed1977

Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors.

Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase.

Adrenal Cortex Neoplasms↗
PubMed1993

In vitro phosphorylation sites of stallion and bull P1-protamines for cyclic adenosine 3',5'-monophosphate-dependent protein kinase and protein kinase C.

Fish and mammalian protamines are phosphorylated after their synthesis during sperm cell maturation. Cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC), both requiring basic amino acids at their recognition sites, have previously been found to phosphorylate fish protamines in vitro. In this study, these enzymes were used to phosphorylate stallion and bull sperm P1-protamines in vitro. A species-specific difference was found, since PKA was able to phosphorylate both protamines while PKC phosphorylated only stallion protamine. Thr-41, the only threonine residue in stallion P1-protamine, and most probably the homologous Thr-43 in bull P1-protamine are the sites for PKA phosphorylation in addition to an internally located Ser-29 present only in stallion protamine. This Ser residue was phosphorylated in vitro by both kinases. Protamine phosphorylation by PKA was found to be almost independent of cAMP and was inhibited only by a tenfold concentration of PKI when compared to phosphorylation of a model peptide, kemptide. Addition of calcium, phosphatidylserine, and diolein caused a twofold stimulation in phosphorylation of stallion protamine by PKC, indicating that specific cofactors of PKC may have a role in mammalian protamine phosphorylation. We suggest that PKA is a good universal candidate for in vivo phosphorylation of P1-protamines.

Amino Acid Sequence↗
PubMed1991

Stimulation of the ATPase activity of rat brain protein kinase C by phospho acceptor substrates of the enzyme.

We recently reported that autophosphorylated rat brain protein kinase C (PKC) catalyzes a Ca2(+)- and phosphatidylserine- (PS-) dependent ATPase reaction. The Ca2(+)- and PS-dependent ATPase and histone kinase reactions of PKC each had a Km app(ATP) of 6 microM. Remarkably, the catalytic fragment of PKC lacked detectable ATPase activity. In this paper, we show that subsaturating concentrations of protein substrates accelerate the ATPase reaction catalyzed by PKC and that protein and peptide substrates of PKC induce ATPase catalysis by the catalytic fragment. At subsaturating concentrations, histone III-S and protamine sulfate each accelerated the ATPase activity of PKC in the presence of Ca2+ and PS by as much as 1.5-fold. At saturating concentrations, the protein substrates were inhibitory. Poly(L-lysine) failed to accelerate the ATPase activity, indicating that the acceleration observed with histone III-S and protamine sulfate was not simply a result of their gross physical properties. Furthermore, histone III-S induced the ATPase activity of the catalytic fragment of PKC, at both subsaturating and saturating histone concentrations. The induction of ATPase activity was also elicited by the peptide substrate Arg-Arg-Lys-Ala-Ser-Gly-Pro-Pro-Val, when the peptide was present at concentrations near its Km app. The induction of the ATPase activity by the nonapeptide provides strong evidence that the binding of phospho acceptor substrates to the active site of PKC can stimulate ATP hydrolysis. Taken together, our results indicate that PKC-catalyzed protein phosphorylation is inefficient, since it is accompanied by Pi production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1999

SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1.

Arginine/serine protein kinases constitute a novel class of enzymes that can modify arginine/serine (RS) dipeptide motifs. SR splicing factors that are essential for pre-mRNA splicing are among the best characterized proteins that contain RS domains. TwoSRprotein-specifickinases, SRPK1 and SRPK2, have been considered as highly specific for the phosphorylation of these proteins, thereby contributing to splicing regulation. However, despite the fact that SR proteins are more or less conserved among metazoa and have a rather ubiquitous tissue distribution we now demonstrate that SRPK1 is predominantly expressed in testis. In situ expression analysis on transverse sections of adult mouse testis shows that SRPK1 mRNA is abundant in all germinal cells but not in mature spermatozoa. RS kinase activity was found primarily in the cytosol and only minimal activity was detected in the nucleus. In a search for testis-specific substrates of SRPK1 we found that the enzyme phosphorylates human protamine 1 as well as a cytoplasmic pool of SR proteins present in the testis. Protamine 1 belongs to a family of small basic arginine-rich proteins that replace histones during the development of mature spermatozoa. The result of this progressive replacement is the formation of a highly compact chromatin structure devoid of any transcriptional activity. These findings indicate that SRPK1 may have a role not only in pre-mRNA splicing, but also in the condensation of sperm chromatin.

Amino Acid Sequence↗
PubMed1992

Temporal gene expression is restored concomitantly with germ cells in the experimentally regressed rat testis.

The present study was designed to examine the effect of hypophysectomy and subsequent testosterone administration on germ cell numbers and germ cell- and Sertoli cell-specific mRNA levels in adult rats. Rats were hypophysectomized and 4 weeks later received 24-cm testosterone-containing polydimethylsiloxane (PDS) implants. Sham-hypophysectomized rats received an empty PDS implant. At 0 and 3 days, and at 1, 2, 4, and 8 weeks, rats were killed. One testis from each rat (n = 4/group) was used to prepare total RNA; the other testis was used to enumerate stage VII-VIII germ cells. cDNA probes for germ cell and Sertoli cell products were used to monitor germ cell- and Sertoli cell-specific mRNAs on Northern blots. Four weeks after hypophysectomy (0 days), preleptotene and pachytene spermatocytes and round and elongating spermatids were reduced in number to 54%, 12%, 1%, and 0%, respectively, of the control values. Testosterone administration caused a time-dependent increase in germ cell numbers; after 8 weeks of testosterone treatment, preleptotene and pachytene spermatocytes and round and elongating spermatids were 75%, 79%, 74%, and 22%, respectively, of control values. Lactate dehydrogenase-C, phosphoglycerate kinase-2, protamine-1, and sulfated glycoprotein-2 mRNA levels (on a per micrograms RNA basis) were 34%, 34%, less than 1%, and 580% of control values, respectively, 4 weeks after hypophysectomy and 79%, 87%, 61%, and 192% of control values, respectively, after 8 weeks of testosterone treatment. Pachytene spermatocyte and round spermatid numbers increased, while Sertoli cell sulfated glycoprotein-2 mRNA levels decreased, with respect to 4 week hypophysectomy values, as early as 3 days after implantation of testosterone capsules. In contrast, germ cell (lactate dehydrogenase-C, phosphoglycerate kinase-2, and protamine-1) mRNA levels increased to the greatest extent between 1-4 weeks after the start of testosterone treatment and, after a short lag period, reflected increases in germ cell type and number. The results indicate that cell-specific mRNAs appear concomitantly with germ cell reappearance in a time-dependent manner in the testes of testosterone-treated hypophysectomized adult rats.

Animals↗
PubMed1980

Quantitation of mRNAs during mouse spermatogenesis: protamine-like histone and phosphoglycerate kinase-2 mRNAs increase after meiosis.

Total RNA, prepared from immature or mature mouse testes or from spermatogenic cells separated on the basis of sedimentation velocity, was translated in vitro. Mouse protamine-like histone could be identified as an in vitro translational product when [3H]arginine was used as the label. The mRNA for protamine-like histone was detected only after meiosis; the appearance of a peak of radioactivity comigrating with protamine-like histone occurred only when RNA from mature testes or late spermatid cell fractions was translated. Phosphoglycerate kinase-2 (ATP:3-phospho-D-glycerate I-phosphotransferase, EC 2.7.2.3) was identified as an in vitro translational product by affinity chromatography followed by two-dimensional gel electrophoresis or by specific immunoprecipitation when [35S]methionine was the label. The mRNA for phosphoglycerate kinase-2 was detected only in mature testes or late spermatid cell fractions. These translational assays for protamine-like histone and phosphoglycerate kinase-2 mRNAs suggest that these messages are transcribed after meiosis.

Animals↗
PubMed1988

Ca2+-independent binding of [3H]phorbol dibutyrate to protein kinase C is supported by protamine and other polycations.

The activity of the Ca2+- and phospholipid-dependent protein kinase, protein kinase C (PKC), can be modulated by diacylglycerols and phorbol esters. The association of these agents with PKC is, in turn, generally understood to be dependent on Ca2+ and phospholipids. Certain substrates, e.g. protamine sulphate, are known to undergo cofactor-independent phosphorylation by PKC. We report here that, in the presence of such substrates, PKC bound 1,2-dihexanoylglycerol and phorbol dibutyrate in a Ca2+-independent manner. Histone IIIs, which is phosphorylated by PKC only in the presence of Ca2+ and phospholipid, also supported Ca2+-independent binding of 1,2-dihexanoylglycerol and phorbol dibutyrate to PKC, but to a lesser extent than did protamine. Support for Ca2+-independent binding was also exhibited by non-peptide polycations (e.g. DEAE-cellulose DE52), indicating that recognition of the catalytic site is not a prerequisite for this effect. The natural polyamines spermine and putrescine did not have this property, however. The affinity of PKC for phorbol dibutyrate and 1,2-dihexanoylglycerol was found to be unchanged by the presence of substrates or DE52. It is proposed that, in the absence of Ca2+, certain polycations favour expression of the diacylglycerol/phorbol ester binding site by stabilizing the active conformation of PKC.

Animals↗
PubMed1994

Differences in tyrosine phosphorylation of oocyte key proteins during 5HT-induced meiosis reinitiation in two bivalve species.

The neurohormone serotonin (5HT) triggers meiosis reinitiation in oocytes of the pelecypod molluscs Spisula solidissima and Ruditapes philippinarum. However, while Spisula oocytes complete maturation, Ruditapes oocytes arrest in metaphase I. Anti-phosphotyrosine antibody revealed that serotonin triggered an early tyrosine phosphorylation of p42mapk which was transient in Spisula, but persisted in Ruditapes. Moreover, dephosphorylation of tyrosine residues of p34cdc2 was only observed in Spisula oocytes, simultaneously with germinal vesicle breakdown. The possibility is discussed that such differences may account for maintenance of the metaphase I block.

Animals↗
PubMed1984

Synthase activation is not a prerequisite for glycogen synthesis in the starved liver.

To evaluate the contribution of phosphorylase and synthase interconversion as well as the availability of substrates to the onset of liver glycogen synthesis, this process was studied in rats starved overnight and refed for 4 h. On feeding, phosphorylase kinase and phosphorylase were inactivated in a cAMP-independent way, but the proportion of synthase a was unchanged and associated with increased hexoses 6-phosphate (glucose and fructose 6-phosphate), uridine diphosphoglucose (UDPG), and fructose 2,6-bisphosphate concentrations. These findings serve to support a "push" mechanism whereby substrate availability for synthase a concerted with phosphorylase inactivation provokes glycogen deposition. Anesthesia was compulsory for liver sampling and analysis. If such experiments were carried out in conscious rats killed by decapitation, artefactual cAMP-dependent phosphorylase activation and synthase inactivation were observed in starved animals. The phosphorylase activation persisted in refed animals but by a cAMP-independent mechanism.

Animals↗
PubMed1993

Smooth muscle cell proliferation. Expression and kinase activities of p34cdc2 and mitogen-activated protein kinase homologues.

Rat vascular smooth muscle cells were synchronized to the quiescent state (G0) by serum deprivation and then stimulated to enter the cell cycle by serum refeeding. At various times of the cell cycle, cells were analyzed for the expression of p34cdc2 and mitogen-activated protein kinase homologues by immunoblotting and for kinase activity toward histone H1, myelin basic protein, and caldesmon. A small amount of p34cdc2 was expressed in the G0/G1 phase (0 to 8 hours). At the G1/S transition (12 hours), the level of p34cdc2 started to accumulate and increased by 60-fold at G2/M (18 hours), accompanied by a more slowly migrating band. Histone H1 kinase activity was undetectable in anti-p34cdc2 immunoprecipitates in the G0/G1 cells but appeared around the G1/S boundary and peaked at G2/M (18 hours). The caldesmon kinase activity exhibited two distinct phases: the first appeared at G0/G1 (0 to 8 hours), and the second appeared at G1/S and continued through G2/M. Two mitogen-activated protein kinase isoforms were expressed throughout the cell cycle. Anti-mitogen-activated protein kinase immunoprecipitates possessed kinase activities toward myelin basic protein and caldesmon, which were activated within 15 minutes after serum stimulation and declined within a few hours. These findings suggest that p34cdc2 and mitogen-activated protein kinase homologues may play significant roles in regulating the progression of the cell cycle of smooth muscle cells, the former at the G2/M transition and the latter at the G0/G1 transition.

Animals↗
PubMed1993

p21ras-induced meiotic maturation of Xenopus oocytes in the absence of protein synthesis: MPF activation is preceded by activation of MAP and S6 kinases.

Microinjection of transforming p21ras into Xenopus oocytes caused a time-dependent increase in the level of total cell protein phosphorylation that culminated with germinal vesicle breakdown (GVBD). The same pattern of phosphorylation was observed in oocytes matured by either progesterone or insulin. Treatment with cycloheximide (CHX) completely blocked both GVBD and the associated de novo phosphorylations induced by the hormones, but did not abolish p21ras-induced maturation nor the occurrence of associated maturation promoting factor (MPF)-dependent and -independent phosphorylations. Thus, induction of GVBD by p21ras in the absence of protein synthesis correlated with the activation of cytosolic MPF-associated kinase activity similar in specificity on exogenous (histone H1) and endogenous (47 kDa and a 42 kDa proteins) substrates to the MPF activity of hormonally-matured oocytes. The injection of p21ras in the presence of CHX caused also activation of other kinase(s) proceeding MPF activation which were responsible for the phosphorylation of endogenous substrates including a 41 kDa protein and a 92 kDa protein kinase that comigrated, respectively, with bands recognized specifically by antibodies to MAP2 kinase and S6 kinase. The phosphorylation of those bands correlated also with the activation of cytosolic kinases acting specifically on myelin basic protein (MBP) and a S6-derived peptide as substrates. These results indicate that, in the absence of protein synthesis, p21ras is able to activate phosphorylation events leading to GVBD and suggest that this oncoprotein can participate in at least two separate pathways of MPF activation. We propose that the activation of MAP/MBP kinases and S6 kinases is an early effect of p21ras oncoproteins.

Animals↗
PubMed1994

Expression of the noncatalytic domain of the NIMA kinase causes a G2 arrest in Aspergillus nidulans.

Temperature-sensitive mutation of the nimA gene of Aspergillus nidulans causes a reversible G2 arrest, whereas overexpression of nimA causes premature entry into mitosis from which the cells cannot exit. The nimA gene encodes a Ser/Thr-specific protein kinase (NIMA) which contains an extended COOH-terminal noncatalytic domain. To evaluate the role of this enzyme in nuclear division control, we introduced various mutant nimA cDNAs under the control of the inducible alcohol dehydrogenase gene promoter into a strain of Aspergillus nidulans containing a temperature-sensitive nimA mutation (nimA5). While expression of the wild type NIMA complemented the nimA5 mutation and induced a premature mitotic arrest when overexpressed, expression of a kinase-negative NIMA containing a single amino acid mutation in the putative ATP-binding site could not rescue the nimA5 mutation but resulted in a specific G2 arrest when overexpressed. An identical phenotype was observed with cells expressing only the noncatalytic COOH-terminal domain of NIMA, whereas overexpression of the inactive kinase domain was without effect. The G2 arrest produced by overexpression of the full-length inactive or COOH-terminal NIMA molecules did not prevent activation of the endogenous NIMA or H1 kinase activity precipitable by p13 beads. We suggest that this dominant-negative phenotype results from competitive inhibition of the association of active NIMA with a cellular target(s) and that appropriate targeting is essential for the mitotic function of the NIMA kinase.

Alcohol Dehydrogenase↗
PubMed1990

Non-histone chromatin proteins in beef thyroid: distinct phosphorylation patterns of several protein kinases.

Non-histone chromatin protein (NHCP) fractions were extracted from purified beef thyroid nuclear preparations and tested for the presence of protein kinase activities using several known mediators of thyroid regulation, as well as potential phosphotransferase substrates using purified or partially purified protein kinase activities. The addition of cAMP/3-isobutyl-1-methylxanthine had no effect on NHCP histone kinase activity; the addition of 10 micrograms of the heat-stable cAMP-dependent protein kinase A inhibitor, however, resulted in a 47% reduction in histone H1 kinase activity. Nuclear casein kinase II activity was present in the NHCP fractions as evidenced by the capacity of spermine to stimulate (ED50 = 0.19 mM) and heparin to inhibit (ID50 = 0.09 microgram/ml) the phosphorylation of casein; further, the phosphotransferase activity could be purified by sequential casein-agarose and spermine-agarose affinity chromatography. Neither calcium-calmodulin nor calcium/phosphatidylserine/diolein had an effect on NHCP casein kinase or histone kinase activities, respectively. The addition of cAMP-dependent protein kinase A catalytic subunit, nuclear casein kinase II, calcium-activated calmodulin-dependent protein kinase and diacylglycerol-activated calcium/phospholipid-dependent protein kinase C activities exhibited distinct phosphorylation patterns when NHCP were used as substrates and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. We conclude that NHCP fraction from beef thyroid: 1) contains both cAMP-dependent protein kinase A catalytic subunit and nuclear casein kinase II and 2) substrates for cAMP-dependent protein kinase A, calcium-activated calmodulin-dependent protein kinase, protein kinase C, and nuclear casein kinase II.

Animals↗
PubMed1996

Co-culture with pig membrana granulosa cells modulates the activity of cdc2 and MAP kinase in maturing cattle oocytes.

Bovine cumulus-enclosed oocytes, initially cultured up to diakinesis (8 h of initial culture) or metaphase I (12 h of initial culture), were subsequently co-cultured for 6 h in contact with pig membrana granulosa (PMG) cells and then assayed for histone H1 and MAP kinase activities. In addition, the phosphorylation state of ERK 1,2 proteins was determined by Western blotting. The alterations in nuclear envelope breakdown, meiotic spindle formation and the patterns of chromosome condensation were analysed by immunofluorescence and transmission electron microscopy. The diakinesis-stage oocytes (initially cultured for 8 h) already possessed high histone H1 kinase and MAP kinase activities that were correlated with condensed and partially individualised chromosomes. The ERK 1 and most ERK 2 proteins were partly phosphorylated. Following the 6 h co-culture of these oocytes with PMG a rapid decrease in MAP kinase activity and a slower decrease in histone H1 kinase occurred, as well as ERK 1 and ERK 2 dephosphorylation. Both kinase activities and ERK 1,2 phosphorylation were fully restored following the release of the oocytes from co-culture and a subsequent culture in the absence of PMG. Moreover, the clumped bivalents were reindividualised and 56% of these oocytes reached metaphase II after 20 h of culture without PMG. The metaphase I oocytes, initially cultured for 12 h, displayed a fusiform meiotic spindle and a metaphase array of chromosomal bivalents, accompanied by high levels of both histone H1 and MAP kinase activity. Co-culture of MI oocytes with PMG abolished the activity of both kinases and caused the dephosphorylation of ERK 1 and ERK 2. Furthermore, the spindle microtubules were depolymerised and the chromosomal bivalents clumped into a single mass. Neither of the protein kinase activities nor the meiotic spindle were restored following subsequent culture in the absence of PMG for up to 20 h. These observations indicate that under in vitro conditions membrana granulosa cells can cause a prompt decrease in histone H1 and MAP kinase activities, and metaphase I oocytes. While these events are fully reversible in late diakinesis oocytes, metaphase I oocytes did not complete maturation after release from co-culture.

Animals↗
PubMed1997

MAP kinase is required for the spindle assembly checkpoint but is dispensable for the normal M phase entry and exit in Xenopus egg cell cycle extracts.

In Xenopus laevis egg cell cycle extracts that mimic early embryonic cell cycles, activation of MAP kinase and MAP kinase kinase occurs in M phase, slightly behind that of maturation promoting factor. To examine the possible role of MAP kinase in the in vitro cell cycle, we depleted the extracts of MAP kinase by using anti-Xenopus MAP kinase antibody. Like in the mock-treated extracts, the periodic activation and deactivation of MPF occurred normally in the MAP kinase-depleted extracts, suggesting that MAP kinase is dispensable for the normal M phase entry and exit in vitro. It has recently been reported that microtubule depolymerization by nocodazole treatment can block exit from mitosis in the extracts if enough sperm nuclei are present, and that the addition of MAP kinase-specific phosphatase MKP-1 overcomes this spindle assembly checkpoint, suggesting the involvement of MAP kinase in the checkpoint signal transduction. We show here that the spindle assembly checkpoint mechanism cannot operate in the MAP kinase-depleted extracts. But, adding recombinant Xenopus MAP kinase to the MAP kinase-depleted extracts restored the spindle assembly checkpoint. These results indicate unambiguously that classical MAP kinase is required for the spindle assembly checkpoint in the cell cycle extracts. In addition, we show that strong activation of MAP kinase by the addition of a constitutively active MAP kinase kinase kinase in the absence of sperm nuclei and nocodazole, induced mitotic arrest in the extracts. Therefore, activation of MAP kinase alone is sufficient for inducing the mitotic arrest in vitro.

Animals↗
PubMed1985

[Change in the protein kinase activity of glandular stomach mucosa in rats during malignant transformation].

Changes in the activity of protein kinases in the glandular stomach mucosa of rat were studied in the case of carcinogenesis induced by N-methyl-N'-nitro-N'-nitrosoguanidine. No essential changes in the activity of cAMP-dependent protein kinase (histone kinase) were found in the mucosa as well as in tissues of the developed tumours of the rat glandular stomach. The activity of cAMP-independent protein kinase (casein kinase) increased significantly 3 months after the beginning of the carcinogen administration and at the late stages (after 12-15 months) it was decreased considerably both in the glandular stomach tumours and in the stomach mucosa without the characters of the malignant growth. It is supposed that changes in the activity of casein kinase in the stomach mucosa at the late carcinogenesis stages are associated with the neoplastic transformation and precede the appearance of morphological characters of the malignization.

Animals↗
PubMed1981

[Human leukemic-cell protein-kinases. 1 - Non-granulocytic leukemias (author's transl)].

The study of human leukemic-cell protein-kinases is justified by two types of arguments: on one hand, abnormal protein-kinases have been found in various malignancies, and on the other the products of virus transforming genes have repeatedly been identified as protein-kinases. Using cytosolic and particulate extracts of normal human lymphocytes we measured protein-kinase activities, then following partial purification by DEAE and phosphocellulose chromatography the isoenzymes of cyclic AMP dependent and independent protein-kinases and casein-kinases were determined in order to establish a profile (12 normal subjects). The same methodology was applied to the lymphocytes of 5 patients with chronic lymphocytic leukemia (CLL) and 3 patients with acute lymphoblastic leukemia (ALL). Compared to normal lymphocytes, the specific activity of cytosolic and particulate extracts from the leukemics was higher for histone and casein-kinases, following elimination of an inhibitory activity present in the crude extracts. Studies of the isoenzymes showed, in some individuals, the presence in both cytosolic and particulate extracts of two important cyclic AMP dependent histone-kinase activities, which were very low or absent in normal lymphocyte extracts. In the particulate extracts we found a constant increase in casein-kinase activities concerning essentially one of the two isoenzymes present. Also, the ratio of the different isoenzymes separated by chromatography was considerably modified with regard to both histone and casein-kinases. These quantitative and qualitative abnormalities were present in some CLL cells and in non-granulocytic acute leukemic cells. They resembled the modification reported during normal lymphocyte stimulation by phytohemagglutinin, and also seemed to reflect the intensity of cellular replication and to some degree the progression of the disease.

Casein Kinases↗