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PubMed1999

MyoD stimulates delta-1 transcription and triggers notch signaling in the Xenopus gastrula.

The Notch signaling cascade is involved in many developmental decisions, a paradigm of which has been the selection between epidermal and neural cell fates in both invertebrates and vertebrates. Notch has also been implicated as a regulator of myogenesis, although its precise function there has remained controversial. Here we show that the muscle-determining factor MyoD is a direct, positive regulator of the Notch ligand Delta-1 in prospective myoblasts of the pre-involuted mesoderm in Xenopus gastrulae. Injection of a dominant MyoD repressor variant ablates mesodermal Delta-1 expression in vivo. Furthermore, MyoD-dependent Delta-1 induction is sufficient to activate transcription from promoters of E(spl)-related genes in a Notch-dependent manner. These results indicate that a hallmark of neural cell fate determination, i.e. the feedback loop between differentiation promoting basic helix-loop-helix proteins and the Notch regulatory circuitry, is conserved in myogenesis, supporting a direct involvement of Notch in muscle determination.

Animals↗
PubMed1995

Modulation of human IGF binding protein-3 activity by structural modification.

To delinate regions of IGFBP-3 involved in ligand and cell-surface binding. DNAs encoding human IGFBP-3 [1-264] and several variants were transfected into CHO cells. Of three deletion (delta) mutants. IGFBP-3 [1-88], [1-184], and [delta 89-184], none bound IGF-I tracer by ligand blotting, although all were detectable by immunoblotting. No ALS binding was detectable, as predicted by the lack of IGF binding. Normal-sequence IGFBP-3 associated with the CHO cells and was partly displaceable by IGF-I. Whereas IGFBP-3 [1-88] and [1-184] failed to cell-associate, the non-IGF-binding central deletion variant [delta 89-184] did associate with CHO cells but was not displaced by IGF-I. To further examine the role of the carboxy-terminal domain in cell-association, the basic sequence IGFBP-3 [228-232] (KGRKR) was altered to the corresponding IGFBP-1 residues MDGEA, a major charge reversal. This variant showed reduced IGF-I binding, and bound ALS with decreased affinity as determined by Scatchard analysis. It showed no cell binding, implicating the basic domain in cell-association. We conclude that, whereas the central and carboxy-terminal domain deletions fail to bind IGF-I, the ability to cell associate requires the carboxy-terminal but not the central domain. Specifically, the basic region [228-232] is essential for cell binding, and also affects IGF-I binding, and independently, ALS affinity.

Amino Acid Sequence↗
PubMed1987

Membrane glycophorins of Dantu blood group erythrocytes.

Glycophorins of erythrocytes of two unrelated individuals who exhibit the Dantu blood group phenotype were studied. Immunoblots indicated that erythrocytes of each individual contained a complement of a normal alpha-glycophorin (glycophorin A) and a variant N-glycophorin. delta-Glycophorin (glycophorin B) was present in one donor's cells but not the other's; the s and N phenotypes of the latter's erythrocytes may derive from the variant glycophorin. The variant glycophorin is of a smaller size, does not bind to Lens culinaris lectin agarose, and lacks residues approximately 40-60 of alpha-glycophorin and its single asparagine-linked carbohydrate; it contains approximately 2 less O-glycosidically bound units whose structures are identical to those found in alpha-glycophorins. All these properties are characteristic of delta-glycophorin. The variant is related to alpha-glycophorin in the carboxyl-terminal region as shown by reaction with a specific antiserum. Sequence analyses of a mixture of chymotryptic peptides of a CNBr fragment of the variant glycophorin identified the sequence Val-His-Arg-Phe-Thr-Val-Pro-Glu-Ile-Thr-Leu-Ile-Ile that contains the junction point of delta- and alpha-glycophorins spanning residues 33-38/39 of delta-glycophorin and residues 71/72-77 of alpha-glycophorin. Sequence analysis of a mixture of CNBr fragments allowed us to conclude that the variant originates from delta-s- rather than delta-S-glycophorin. The quantity of the variant Dantu glycophorin when compared to alpha-glycophorin differed in the two individuals, the ratio being 2/1 in one individual's cells and 0.5/1 in the other's. This may reflect that the two donors belong to different varieties of Dantu phenotypes. Together, the evidence indicates that both donors' erythrocytes contain a (delta-alpha) variant glycophorin, whose amino terminus originates from delta-s-glycophorin and the carboxyl end from alpha-glycophorin with a junction point around residues 39 of delta- and 71 of alpha-glycophorins. The results suggest that the unique junction region may be characteristic of the Dantu phenotype.

Amino Acid Sequence↗
PubMed1996

Molecular cloning, splice variants, expression, and purification of phospholipase C-delta 4.

Complementary DNAs encoding a previously unidentified phosphoinositide-specific phospholipase C (PLC) isozyme were cloned from a rat brain cDNA library by the polymerase chain reaction with degenerate oligonucleotide primers based on sequences common to three known delta-type PLC isozymes. The encoded polypeptide contains 772 amino acids (calculated molecular mass, 88,966 daltons) and is similar in primary structure to delta-type PLC isozymes, with overall sequence identities of 45% to PLC-delta 1, 72% to PLC-delta 2, and 47% to PLC-delta 3. Thus, the new PLC isozyme was named PLC-delta 4. Recombinant PLC-delta 4 was purified from extracts of HeLa cells that had been infected with vaccinia virus containing the corresponding cDNA. The purified protein exhibited an apparent molecular mass of 90 kDa on SDS-polyacrylamide gels. The specific activity of PLC-delta 4 and its dependence on Ca2+ were similar to those of PLC-delta 1. The distribution of PLC-delta 4 in 16 different rat tissues was studied by immunoblot analysis with PLC-delta 4-specific antibodies of fractions obtained after an enzyme-enrichment procedure. The 90-kDa immunoreactive protein was detected unambiguously in only eight tissues and was present at concentrations that were low compared to those of other major PLC isozymes. A 93-kDa immunoreactive protein was also prominent in testis but was not detected in the other seven positive tissues. The 93-kDa enzyme appears to be derived from a splice variant of the mRNA that encodes the 90-kDa PLC-delta 4 and contains an additional 32 amino acids between the X and Y catalytic domains. Splice variants have not previously been detected for delta-type PLC isozymes.

Alternative Splicing↗
PubMed2004

A strain-specific alteration of proteomic expression in mouse liver fructose 1,6-bisphosphatase isoforms by alcohol.

To study alcohol-related metabolism across inbred mouse strains, liver tissues from C57BL/6J (B6, an alcohol-preferring mouse) and DBA/2J (D2, an alcohol-avoiding strain) mice were analyzed for proteomic expression patterns over time after a single-dose of alcohol (1.5 g/kg ingestion). Despite no significant difference in the elimination rate of blood ethanol, two-dimensional electrophoresis gel images of liver proteins showed that proteins in B6 mice exhibited faster response and more quantitative (spot numbers) and qualitative (spot densities) changes than in D2 mice. Among the differentially expressed metabolic enzymes, four variants (alpha, beta, gamma and delta) of fructose 1,6-bisphosphatase (FBPase), a key regulatory gluconeogenic enzyme, showed remarkable changes in expression with time across the strains. The degree of spot alteration in alpha- and gamma-variants of FBPase in B6 mice was much higher than in D2 mice, while the beta- and delta-forms were not changed as much. Mass spectrometry (MS) analysis showed that the 1714.9 +/- 1 mass peak from the alpha- and gamma-variants of FBPase was much stronger than that of the beta- and delta-variants in both strains regardless of spot density. This MS peak contains 2-ANHAPFETDISTLTR-16, located at the N-terminal of FBPase, where the N-terminal alanine was found to be trimethylated. Thus, we propose this N-terminal fragment as a potential site for enzyme modification in response to ethanol, allowing for differences in two-dimensional gel spot intensity of variants of FBPase in the two mouse strains.

Animals↗
PubMed1997

Abnormal microheterogeneity detected in one commercial alpha 1-acid glycoprotein preparation using chromatography on immobilized metal affinity adsorbent and on hydroxyapatite.

The study of one commercial preparation of human alpha 1-acid glycoprotein (AAG) by isoelectric focusing and by different chromatographic methods, previously developed to purify and fractionate the genetic variants of AAG, revealed an abnormal heterogeneity for this preparation. In addition to the three main variants (F1, S and A) of AAG normally present, this preparation contained five other AAG variants (called here sigma, alpha, beta, delta and gamma), accounting for ca. 40% of the total. As it is very unlikely that the latter variants are rare AAG variants, the abnormal heterogeneity of this AAG preparation is most probably due to structural alterations occurring during the large scale isolation. The alpha and the sigma, beta, delta and gamma variants could correspond to altered forms of the A and the F1 and S variants, respectively, because of their similar retention behaviour on immobilized copper(II) ions and their similar drug binding properties. However, the elution of the variants from the immobilized metal affinity column suggested that sigma, alpha, beta, delta and gamma were desialylated. Chromatography on hydroxyapatite enabled the separation of the F1, S and A variants from the sigma, alpha, beta, delta and gamma variants. The inability of the latter variants to bind to hydroxyapatite suggests that the structural alterations might involve acidic amino acid residues. This proposal agreed with the isoelectric focusing study of variants sigma, alpha, beta, delta and gamma. Since the different separation methods used were able to resolve the variants of this AAG, this protocol could be used for characterization of commercial AAG proteins.

Animals↗
PubMed2024

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics.

Both host and viral RNA editing plays a crucial role in host's response to infection, yet our understanding of host RNA editing remains limited. In this study of in-house generated RNA sequencing (RNA-seq) data of 211 hospitalized COVID-19 patients with PreVOC, Delta, and Omicron variants, we observed a significant differential editing frequency and patterns in long non-coding RNAs (lncRNAs), with Delta group displaying lower RNA editing compared to PreVOC/Omicron patients. Notably, multiple transcripts of UGDH-AS1 and NEAT1 exhibited high editing frequencies. Expression of ADAR1/APOBEC3A/APOBEC3G and differential abundance of repeats were possible modulators of differential editing across patient groups. We observed a shift in crucial infection-related pathways wherein the pathways were downregulated in Delta compared to PreVOC and Omicron. Our genomics-based evidence suggests that lncRNA editing influences stability, miRNA binding, and expression of both lncRNA and target genes. Overall, the study highlights the role of lncRNAs and how editing within host lncRNAs modulates the disease severity.

Biological sciences↗
PubMed1998

Characterization of cucumber mosaic virus. V. Cell-to-cell movement requires capsid protein but not virions.

To ascertain the importance of amino-terminal proximal capsid protein (CP) sequences in cel-to-cell movement, virion formation, and stabilization, two CP mutants of cucumber mosaic virus (CMV) were generated by deletion of sequences encoding CP amino acids 15-40 (delta Sal-Nru) or 26-40 (delta Sac-Nru). Wildtype CMV and CMV containing delta Sac-Nru could infect systemically four host species, although symptoms induced by the two viruses usually were different CMV containing delta Sal-Nru could only infect Nicotiana benthamiana and N. clevelandii systemically, but only slowly, suggesting phloem-independent long-distance movement. A variant mutant designated delta Sal-Nru* could systemically infect N. tabacum as well as the above two Nicotiana species, rapidly, but could not systemically infect Cucurbita pepo. Virus particles could not be detected in plants infected by delta Sal-Nru, while delta Sal-Nru* and delta Sac-Nru formed particles of lower stabilities than for wildtype virus. The CPs of delta Sal-Nru and delta Sal-Nru* could bind RNA in vitro, although less strongly than delta Sac-Nru or wildtype CMV. These data indicate that amino-terminal proximal sequences of the CMV CP interact with viral RNA and are required for the formation of stable virions. Moreover, while the CP is necessary for cell-to-cell movement, the ability to form virions is not a prerequisite for cell-to-cell movement.

Amino Acid Sequence↗
PubMed1999

Abnormal, error-prone bypass of photoproducts by xeroderma pigmentosum variant cell extracts results in extreme strand bias for the kinds of mutations induced by UV light.

Xeroderma pigmentosum (XP) is a rare genetic disease characterized by a greatly increased susceptibility to sunlight-induced skin cancer. Cells from the majority of patients are defective in nucleotide excision repair. However, cells from one set of patients, XP variants, exhibit normal repair but are abnormally slow in replicating DNA containing UV photoproducts. The frequency of UV radiation-induced mutations in the XP variant cells is significantly higher than that in normal human cells. Furthermore, the kinds of UV-induced mutations differ very significantly from normal. Instead of transitions, mainly C-->T, 30% of the base substitutions consist of C-->A transversions, all arising from photoproducts located in one strand. Mutations involving cytosine in the other strand are almost all C-->T transitions. Forty-five percent of the substitutions involve thymine, and the majority are transversions. To test the hypothesis that the UV hypermutability and the abnormal spectrum of mutations result from abnormal bypass of photoproducts in DNA, we compared extracts from XP variant cells with those from HeLa cells and a fibroblast cell strain, MSU-1.2, for the ability to replicate a UV-irradiated form I M13 phage. The M13 template contains a simian virus 40 origin of replication located directly to the left or to the right of the target gene, lacZalpha, so that the template for the leading and lagging strands of DNA replication is defined. Reduction of replication to approximately 37% of the control value required only 1 photoproduct per template for XP variant cell extracts, but approximately 2.2 photoproducts for HeLa or MSU-1.2 cell extracts. The frequency of mutants induced was four times higher with XP variant cell extracts than with HeLa or MSU-1.2 cell extracts. With XP variant cell extracts, the proportion of C-->A transversions reached as high as 43% with either M13 template and arose from photoproducts located in the template for leading-strand synthesis; with HeLa or MSU-1.2 cell extracts, this value was only 5%, and these arose from photoproducts in either strand. With the XP variant extracts, 26% of the substitutions involved thymine, and virtually all were T-->A transversions. Sequence analysis of the coding region of the catalytic subunit of DNA polymerase delta in XP variant cell lines revealed two polymorphisms, but these do not account for the reduced bypass fidelity. Our data indicate that the UV hypermutability of XP variant cells results from reduced bypass fidelity and that unlike for normal cells, bypass of photoproducts involving cytosine in the template for the leading strand differs significantly from that of photoproducts in the lagging strand.

Cell Extracts↗
PubMed1988

Thai (delta beta)0-thalassemia and its interaction with gamma-thalassemia.

A variant of Southern Italian (delta beta)0-thalassemia is described in a women of Thai origin. The 3' breakpoint in Thai (delta beta)0-thalassemia is located about 1 kb upstream to that in Southern Italian (delta beta)0-thalassemia and produces a smaller deletion of approximately equal to 12.5 kb. Hematological phenotype, particularly Hb F output, is similar to that found in G gamma A gamma(delta beta)0-thalassemia despite the presence of a coexistent gamma-thalassemia effect.

Chromosome Deletion↗
PubMed1992

Rat pituitary cells selectively express mRNA encoding the short isoform of the y2 GABAA receptor subunit.

The GABAA receptor belongs to the ligand-gated ion channel receptor superfamily and appears to be composed of from 4 to 5 subunits which interact with each other. Molecular cloning of cDNAs encoding the different subunits of the GABAA receptor has revealed an unexpected heterogeneity which includes at least 4 homologous classes of subunits: these classes, designated as alpha, beta, gamma, and delta contain multiple variants. We have measured the steady-state levels of mRNAs encoding different (alpha 1, alpha 4, beta 1, beta 2, beta 3, gamma 2 long, gamma 2 short and delta) GABAA receptor subunits in the rat anterior pituitary and cerebellum using a polymerase chain reaction (PCR)-derived method. We found that pituitary cells express mRNAs encoding the alpha 1, beta 1 and beta 3 GABAA receptor subunits whereas the transcripts for alpha 4, beta 2 and delta were undetectable. We also found that pituitary cells selectively express the short isoform of the gamma 2 subunit mRNA. These data indicate that the expression of the various GABAA receptor subunits is cell-specific and support the concept that the diversity in function and pharmacology of the GABAA receptor is based on the ability of cells to specify the expression of selective GABAA receptor subunits.

Animals↗
PubMed1997

Post-translational modifications and multiple tubulin isoforms in Nicotiana tabacum L. cells.

Distribution of post-translationally modified tubulins in cells of Nicotiana tabacum L. was analysed using a panel of specific antibodies. Polyglutamylated, tyrosinated, nontyrosinated, acetylated and delta 2-tubulin variants were detected on alpha-tubulin subunits; polyglutamylation was also found on beta-tubulin subunits. Modified tubulins were detected by immunofluorescence microscopy in interphase microtubules, preprophase bands, mitotic spindles as well as in phragmoplasts. They were, however, located differently in the various microtubule structures. The antibodies against tyrosinated, acetylated and polyglutamylated tubulins gave uniform staining along all microtubules, while antibodies against nontyrosinated and delta 2-tubulin provided dot-like staining of interphase microtubules. Additionally, immunoreactivity of antibodies against acetylated and delta 2-tubulins was strong in the pole regions of mitotic spindles. High-resolution isoelectric focusing revealed 22 tubulin charge variants in N. tabacum suspension cells. Immunoblotting with antibodies TU-01 and TU-06 against conserved antigenic determinants of alpha- and beta-tubulin molecules, respectively, revealed that 11 isoforms belonged to the alpha-subunit and 11 isoforms to the beta-subunit. Whereas antibodies against polyglutamylated, tyrosinated and acetylated tubulins reacted with several alpha-tubulin isoforms, antibodies against nontyrosinated and delta 2-tubulin reacted with only one. The combined data demonstrate that plant tubulin is extensively post-translationally modified and that these modifications participate in the generation of plant tubulin polymorphism.

Acetylation↗
PubMed1982

Immunoglobulin V region variants in hybridoma cells. II. Recombination between V genes.

The mouse hybridoma line B1-8.delta 1 secretes a monoclonal IgD, lambda 1 anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody with defined idiotypic determinants. Two spontaneous V-region variants (B1-8.V1/V2) with altered idiotope pattern were selected and the structural variation was located to the variable region of the heavy chain. The amino acid sequences of the B1-8. delta 1 and variant heavy chain V regions were determined. The variant VH regions are identical. Wild-type and variant VH regions differ in 10 positions. Single amino acid exchanges are found in the first and second framework at positions 20 and 43. The majority of replacements (eight substitutions) is clustered in the second complementary-determining region (CDR 2). There are no differences in CDR 1 and CRD 3 and the JH region. The variant, which at first glance appears to have undergone a series of point mutations, arose by recombination, possibly gene conversion, between the rearranged VDJ gene of the wild-type (B1-8.delta 1) and a neighbouring germ line VH gene encoding all of the substitutions.

Amino Acid Sequence↗
PubMed1998

Differentiation-dependent expression of cardiac delta-CaMKII isoforms.

Despite their important role in controlling the cardiac Ca2+ homeostasis, presence and functions of individual isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in the heart are not well studied. Here we report on expression of isoforms of the delta class in two differentiation states of the embryonic rat heart-derived cell line H9c2 compared to adult rat heart. Reverse transcription coupled polymerase chain reaction analysis revealed specific expression patterns of four variants of the delta class (delta B, delta C, delta 4, delta 9) in adult rat heart, H9c2 myoblasts, and skeletal muscle-like H9c2 myotubes. delta C was identified as a common isoform with higher amounts in H9c2 cells and the prominent one in myoblasts. In contrast, expression of delta 9 accompanied cardiac as well as skeletal muscle differentiation. Expression of delta B, however, was representative for differentiated cardiac muscle, whereas delta 4 expression coincided with differentiation into the skeletal muscle-like state. Our results demonstrate differentiation-dependent isoform expression of the delta class of the multifunctional Ca2+/calmodulin-dependent protein kinase of muscle. The identification of cardiac target proteins for this kinase, e.g. the alpha 1-subunit of the L-type Ca2+ channel, the sarcoplasmic reticulum Ca(2+)-ATPase, phospholamban and the ryanodine receptor define H9c2 myoblasts as a suitable model system for further functional characterization of the identified cardiac delta isoforms.

Animals↗
PubMed1992

An association between ADH protein levels and polymorphic nucleotide variation in the Adh gene of Drosophila melanogaster.

Southern analysis of the Adh region of 212 Drosophila melanogaster lines collected from the Tahbilk winery revealed linkage disequilibrium between a 37-bp insertion [designated delta 2 by Kreitman (1983)] and the fast electrophoretic variant of alcohol dehydrogenase (ADH-F). Among these lines 34% contained the insert and encoded ADH-F, 33.5% encoded ADH-F and did not have the insert, and 32.5% encoded the slow electrophoretic variant of alcohol dehydrogenase (ADH-S). Strong linkage association between this insert and ADH-F is evident worldwide. Twenty-nine of the second chromosome lines were characterized for ADH protein quantity by using radial immunodiffusion. ADH quantity was estimated in both larvae and adult males raised in the presence and absence of alcohol supplement to each of two different food media. Analyses of variance indicated higher levels of ADH protein in larvae from lines with the insert (all ADH-F), compared with those without (both ADH-F and ADH-S), independent of either dietary alcohol or media type. No such difference in ADH quantity between insert- and noninsert-containing ADH-F lines was detected in adults, although the expected higher levels occurred in ADH-F lines compared with ADH-S lines. Given the high levels of linkage disequilibrium in the Adh region, these data suggest that either polymorphic nucleotide-site variants positively associated with delta 2 on the second chromosome or delta 2 itself increases larval levels of ADH protein.

Alcohol Dehydrogenase↗
PubMed1995

Leukaemogenesis by the delta Mo + SV Moloney murine leukaemia virus (M-MuLV) variant in E mu pim-1 transgenic mice: high frequency of recombination with a solo endogenous M-MuLV LTR in vivo.

We previously described an enhancer variant of Moloney murine leukaemia virus (M-MuLV), delta Mo + SV M-MuLV, in which the enhancers of MuLV have been deleted and replaced with the enhancers of the simian virus 40 (SV40). When this virus is injected into neonatal NIH Swiss mice, pre-B and B-lymphoblastic lymphomas develop with a latency of 17 months. Van Lohuizen et al. (1989) described a line of transgenic mice that carry an activated pim-1 proto-oncogene transgene (E mu pim-1). They also reported that E mu pim-1 transgenic mice show greatly accelerated lymphoma development when infected with wild-type M-MuLV at birth. In these experiments, neonatal E mu pim-1 transgenic mice were infected intraperitoneally with delta Mo + SV M-MuLV. Marked acceleration of T-lymphoid leukaemia was seen. However, 10 of the 11 tumours analysed were found to be negative for the SV40 enhancers, but they still contained M-MuLV DNA as measured by Southern blot analysis. The LTRs on viruses cloned from two such tumours (as well as on virus recovered by infection onto NIH 3T3 cells) were characterized by PCR amplification, molecular cloning and sequence analysis. The LTR's from the two tumours were identical to each other and were distinct from both the delta Mo + SV M-MuLV and wild-type M-MuLV LTRs. However, they were identical to a rearranged solo M-MuLV LTR present in the E mu pim-1 transgene. These results indicate that the recombination in vivo between delta Mo + SV M-MuLV and the E mu pim-1 transgene yielded a replication-competent and pathogenic virus at high efficiency. This is the first report of in vivo recombination between an exogenous MuLV and a solo endogenous LTR.

Animals↗
PubMedDate not supplied

Looking for GABA in all the wrong places: the relevance of extrasynaptic GABA(A) receptors to epilepsy.

It comes as no surprise that a high concentration of gamma-aminobutyric acid (GABA)(A) receptors exists across the synapse from presynaptic terminals that contain GABA. Oddly, though, many GABA(A) receptors also are far away from synapses. These extrasynaptic GABA(A) receptors are tonically activated by the low levels of GABA normally present in the extracellular space. Many of these extrasynaptic GABA(A) receptors contain the delta subunit. This subunit confers molecular properties on GABA(A) receptors that are well suited for a function in tonic inhibition, with a high affinity for GABA and little desensitization to continuous activation. Recent data linked a genetic variant of the delta subunit to epilepsy, providing a missing link between tonic inhibition and control of brain excitability.

Journal Article↗
PubMed1990

An active site of growth hormone for eliciting the differentiation of preadipose 3T3-F442A cells to adipose cells.

In order to elucidate the active sites of growth hormone for eliciting the differentiation of preadipose 3T3-F442A cells to adipocytes, four artificial mutant variants of human growth hormone (hGH) modified in the loop region of amino acid residues 54-74 were prepared in Escherichia coli by site-directed mutagenesis. Although the P59A (replacement of Pro59 with Ala) variant retained almost the same biological- and receptor binding-activity as hGH, the P61A (replacement of Pro61 with Ala) and the P59A-P61A (replacement of both Pro59 and Pro61 with Ala) both exhibited about half the activity, and the delta (62-67) variant (deletion of the residues 62-67) exhibited only about 0.1% the activity of those of intact hGH. The results suggest that Pro61 may be involved in formation of the active conformation of hGH, but Pro59 may not, and that the amino acid residues around 62-67 may be critical for the specific biological features of hGH.

Adipose Tissue↗