Janus kinase 2 | Kickoff

Janus kinase 2

30 Mar

Janus kinase 2

Janus kinase 2 a protein kinase (q.v.) that func- tions in cellular signal transduction (q.v.). Janus ki- nases phosphorlyate specific tyrosine residues in sub- strate proteins. The gene (JAK 2) which encodes the enzyme is located at 9p24. One function of the JAK 2 protein is to control the responses of erythroblasts to erythropoietin (q.v.). Base substitutions at certain positions in the JAK 2 gene cause polycythemia vera (q.v.). Japanese quail See Coturnix coturnix japonica. jarovization synonym for vernalization (q.v.). jaundice yellowing of the skin, whites of the eyes, and certain body fluids due to abnormally high levels of bilirubin (q.v.) in the blood. See Crigler-Najjar syn- drome, hereditary spherocytosis (HS). Java man an extinct subspecies of primitive man known from fossils obtained in central Java. Now classified as Homo erectus erectus, but formerly re- ferred to as Pithecanthropus erectus. J chain a small protein of about 15,000 daltons that holds the monomeric units of a multimeric im- munoglobulin together, as occurs in the classes IgM and IgA. Jews those people who belong to the ancient Near Eastern Hebrew tribe, the Israelites; also those who trace their descent to Israelites by genealogy or reli- gious conversion to Judaism. Recently an analysis was made of Y-chromosome markers from males who belonged to various Jewish and Moslem popu- lations residing in Europe and North Africa and on the Arabian Peninsula.

The results show that the geographically dispersed Jewish communities closely resemble not only one another but also Palestinians, Syrians, and Lebanese. This analysis suggests that all populations are descended from a common ancestral tribe that lived in the Middle East about 4,000 years ago. See Appendix C, 2000, Hammer et al.; Ash- kenazi. J genes a tandem series of four or five homologous nucleotide sequences coding for part of the hyper- variable regions of light and heavy chains of mouse or human immunoglobulins; so named because they help join one of the genes for the variable region up- stream to one of the genes for the constant region downstream and therefore are an important part of the mechanism generating antibody diversity. JH juvenile hormone. See allatum hormones. Jordan rule an evolutionary principle put forth by the German entomologist Karl Jordan in 1905. It states that closely related species or subspecies are generally adjacent, but separated by a natural barrier (such as a river) that neither can cross easily. jumping genes mobile or “nomadic” genetic enti- ties such as insertion elements and transposons. junctional complex a term used in electron mi- croscopy to refer to any specialized region of inter- cellular adhesion, such as a desmosome (q.v.).

junctional sliding a term descriptive of the fact that the location of intron-exon junctions is not con- stant within members of a gene family, such as the serine proteases. Some variation in length of such gene products can be attributed to extension or con- traction of exons at the intron junctions. junk DNA a term sometimes used to refer to the majority of the DNA in most eukaryotic genomes which does not seem to have a coding or regulatory function. Like “junk,” it is of questionable value, but is not thrown out. See Alu family, selfish DNA, skele- tal DNA hypothesis. Jurassic the middle period in the Mesozoic era, during which the dinosaurs became the dominant land vertebrates. Flying reptiles called pterosaurs evolved, and the first birds appeared. Archaic mam- mals persisted. Ammonites underwent great diversi- fication, and teleost fishes made an appearance. The fragments formed from Pangea began to separate. See Archaeopteryx, continental drift, geologic time di- visions. juvenile hormone See allatum hormones.

K 1. degrees Kelvin. See temperature. 2. Creta- ceous. 3. potassium. 4. the gene in Paramecium aure- lia required for the maintenance of kappa. 5. carry- ing capacity (q.v.). kairomone a trans-specific chemical messenger the adaptive benefit of which falls on the recipient rather than the emitter. Kairomones are commonly nonadaptive to the transmitter. For example, a se- cretion that attracts a male to the female of the same species may also attract a predator. See allomone. Kalanchoe a genus of succulent plants studied in terms of the genetic control of photoperiodic flow- ering response. See phytochrome. kanamycin an antibiotic that binds to the 70S ri- bosomes of bacteria and causes misreading of the mRNA. K and r selection theory See r and K selection theory. kangaroo rat See Dipodomys ordii. K antigens See O antigens. kappa symbiont See killer paramecia. karyogamy the fusion of nuclei, usually of the two gametes in fertilization; syngamy. karyokinesis nuclear division as opposed to cyto- kinesis (q.v.). karyolymph nucleoplasm (q.v.). karyon nucleus (q.v.). karyoplasm nucleoplasm (q.v.).

karyosome a Feulgen-positive body seen in the nucleus of the Drosophila oocyte during stages 3-13. During stages 3-5, it contains synaptonemal com- plexes. karyosphere the condensed Feulgen-positive mass seen in the anterior, dorsal portion of the mature primary oocyte of Drosophila melanogaster. This mass of DNA is not surrounded by a nuclear enve- lope. The tetrads subsequently emerge from the karyosphere and enter metaphase of the first meiotic division. The karyosphere stage of oogenesis is the most radiation-sensitive one. karyotheca nuclear envelope (q.v.). karyotype the chromosomal complement of a cell, individual, or species. It describes the light micro- scopic morphology of the component chromosomes, so that their relative lengths, centromere positions, and secondary constrictions can be identified. Atten- tion is called to heteromorphic sex chromosomes. The karyotype is often illustrated with a figure show- ing the chromosomes placed in order from largest to smallest. This illustration, called an idiogram, may be constructed by aligning photomicrographs of indi- vidual chromosomes, or it may be an inked drawing summarizing the data from a series of analyses of chromosome spreads.

See human mitotic chromo- somes. kb See kilobase. KB cells a strain of cultured cells derived in 1954 by H. Eagle from a human epidermoid carcinoma of the nasopharynx. kbp kilobase pairs. K cells killer cells that mediate antibody-depen- dent cellular cytotoxicity (ADCC). These cells and natural killer (NK) cells have many similar proper- ties, and may belong to the same cell lineage (lym- phocyte or monocyte). Neither K nor NK cells have surface markers characteristic of either T cells (sheep red blood cell receptors) or B cells (endogenous sur- face immunoglobulins). Both K and NK cells possess Fc receptors for class Ig immunoglobulins and thus may acquire membrane-bound antibodies that react with target cells bearing the corresponding antigens. K cells cannot exhibit cytotoxicity without their bound antibodies; NK cells are not so restricted. Prior contact with the antigen is required by the host in order to arm its K cells with antibodies effective in ADCC. kDa kilodalton. See dalton. kDNA kinetoplast DNA. See kinetoplast. kelch (kel) a Drosophila gene on chromosome 2L at 36D3. It encodes an actin-binding protein that is characterized by the presence of six 50-amino acid kelch repeats. The phosphorylation of the kelch pro-

tein is required for the proper morphogenesis of ovarian ring canals (q.v.), and a protein kinase en- coded by Src gene catalyzes this reaction. See actin, Src. Kell-Cellano antibodies antibodies against the red-cell antigens specified by the K gene, named for the first patient known to produce them. See blood groups. kelp the largest of the seaweeds. The giant kelps of the genus Macrocystis reach lengths of 100 meters and form great forests in shallow oceans. See agar, agarose, Phaeophyta. keratins a family of insoluble, cystine-rich intra- cellular proteins that are a major component of epi- dermal coverings such as hair, fur, wool, feathers, claws, hoofs, horns, scales, and beaks. There are many types of keratins, encoded by a large family of genes. Epidermal cells produce a sequence of differ- ent keratins as they mature. In humans, there are more than 20 different keratins synthesized by epi- thelial cells.

Mutations in keratin genes cause heredi- tary blistering diseases in humans and feather defects in chickens. The fibroin of insect silk also belongs to the keratin family. See dominant negative mutation, epidermolysis bullosa, frizzle, intermediate filaments, silk. kernel the seed of a cereal plant such as corn or barley. The sectioned kernel shown below could be any one of the thousand or so found on a corn ear. Each kernel consists of a relatively small diploid em- bryo, a triploid endosperm, and a tough diploid layer of maternal origin, the pericarp. The surface cells of the endosperm contain aleurone grains and oil. The remaining cells contain starch. The scutellum serves to digest and absorb the endosperm during the growth of the embryo and seedling. See anthocyanines, vac- uoles.

keto forms of nucleotides See tautomeric shift. keV See electron volt. Kidd blood group a blood group defined by a hu- man red cell antigen encoded by the JK gene at 18q 11-12. It is about 30 kb long and encodes an integral membrane glycoprotein that functions in the trans- port of urea. The antibody was discovered in 1951 and given the family name of the female patient who produced it. killer paramecia paramecia that secrete into the medium particles that kill other paramecia. The killer trait is due to kappa particles, which reside in the cytoplasm of those strains of Paramecium aurelia syngen 2 that carry the dominant K gene. Later it was found that kappa particles were symbiotic bac-


killer particle

Klenow fragment


exonuclease activity of intact DNA polymerase I is disadvantageous. See Appendix C, 1971, Klenow; DNA polymerase. Klinefelter syndrome (KS) a genetic disease that produces sterile males with small testes lacking sperm. Dr. Harry Klinefelter accurately described the condition in 1943, but the underlying chromo- somal abnormality was not discovered until 1959. The most common karyotype is XXY AA. Less common variations such as XXYY and XXXY also occur. KS demonstrated that maleness in humans depends on the presence of the Y, not the number of X chromosomes. KS appears once in every 500 to 1,000 live-born males. Aside from their sterility, most KS males lead normal healthy lives, although some are mildly retarded. See Appendix C, 1959, Ja- cobs and Strong. Km the Michaelis constant (q.v.). knife breaker a mechanical apparatus that pro- vides a method for breaking strips of plate glass first into squares and then into triangles. These are used as knives against which plastic-embedded tissues are cut into ultrathin sections for observation under the electron microscope. See ultramicrotome.

knob in cytogenetics, a heavily staining enlarged chromomere that may serve as a landmark, allowing certain chromosomes to be identified readily in the nucleus. In maize, knobbed chromatids preferen- tially enter the outer cells of a linear set of four megaspores during megasporogenesis and are there- fore more likely to be included in the egg nucleus (see meiotic drive); genetic markers close to a knob tend to appear more frequently in gametes than those far from a knob. knockout an informal term coined for the genera- tion of a mutant organism (generally a mouse) con- taining a null allele of a gene under study.

Usually the animal is genetically engineered with specified wild-type alleles replaced with mutated ones. The URL for the Mouse knockout database is http://re- search.bmn.com/mkmd. See gene targeting, homolo- gous recombination. Knudson model the “two hit” model of carcino- genesis invented by Alfred K. Knudson to explain clinical-epidemiological observations on retinoblas- toma (q.v.).

This revolutionary concept proposed that certain cancers were caused, not by the pres- ence of an oncogene, but by the absence of an anti- oncogene. In the case of retinoblastoma, children with both eyes affected had a germ-line mutation that predisposed them to the disease. However, a second “hit” or mutation was needed to produce the cancer. Patients without the germ-line mutation re- quired two hits. Extra time was required to acquire the first of the two mutations, and so children with hereditary retinoblastoma developed the disease in both eyes or at multiple sites in one eye, whereas children lacking the RB gene developed single tu- mors and at a later age. See Appendix C, 1971, Knudson. Kornberg enzyme the DNA polymerase isolated from E. coli in 1959 by a group led by A. Kornberg; now called DNA polymerase I; it functions mainly in repair synthesis (q.v.). Krebs cycle a synonym for the citric acid cycle (q.v.).

It was named to honor Hans Adolph Krebs, the biochemist who discovered it. See Appendix C, 1937, Krebs. K strategy a type of life cycle relying on finely tuned adaptation to local conditions rather than on high reproductive rate. See r and K selection theory. Kupffer cells phagocytotic macrophages residing in the liver and first described by the German histol- ogist K. W. von Kupffer in 1876.

kurtosis the property of a statistical distribution that produces a steeper or shallower curve than a normal distribution (q.v.) with the same parameters. kuru a chronic, progressive, degenerative disorder of the central nervous system found in the Fore na- tives living in a restricted area of New Guinea. The disease was at one time thought to be genetically de- termined, but it is now believed to be caused by a prion (q.v.). kV kilovolt (q.v.). kwashiorkor a severe nutritional disorder due to a deficiency of certain amino acids (especially lysine). Kwashiorkor occurs in humans that subsist on a diet of cereal proteins deficient in lysine. See opaque-2.

L 1. line. 2. levorotatory. 3. liter. label the attachment of any substance to a cell or molecule of interest that allows these targets to be readily identified, quantitated, and/or isolated from all other objects in either an in vitro or an in vivo system. Commonly used labels are dyes, fluorescent compounds, enzymes, antibodies, and radioactive el- ements of compounds. Labels are sometimes re- ferred to as tags. label, electron dense See ferritin. label, heavy a heavy isotopic element introduced into a molecule to facilitate its separation from oth- erwise identical molecules containing the more com- mon isotope. See Appendix C, 1958, Meselson and Stahl. lac operon in E. coli, a DNA segment about 6,000 base pairs long that contains an operator sequence and the structural genes lac Z, lac Y, and lac A.

The structural genes code for beta galactosidase, beta galactoside permease, and beta galactoside transace- tylase, respectively. The three structural genes are transcribed into a single mRNA from a promoter ly- ing to the left of the operator. Whether or not this mRNA is transcribed depends upon whether or not a repressor protein is bound to the operator, a regu- latory sequence of 24 base pairs. The repressor pro- tein is encoded by lac I, a gene lying to the left of the lac promoter.

Beta galactosidase (q.v.) catalyzes the hydrolysis of lactose (q.v.) into glucose and ga- lactose. After glucose and galactose are produced, a side reaction occurs, forming allolactose. This is the inducer that switches on the lac operon. It does so by binding to the repressor and inactivating it. See Appendix C, 1961, Jacob and Monod; 1969, Beck- with et al; IPTG, lac repressor, ONPG, polycistronic mRNA, regulator gene, reporter gene. lac repressor the protein that regulates the lac op- eron in E. coli. The protein is the product of the lac I gene and functions as a molecular switch in re- sponse to inducer molecules.

A single bacterium contains only 10 to 20 lac repressor molecules. Each is a homotetramer of Mr 154,520. The monomeric subunit has 360 amino acids, and its structure is dia- grammed in A, below. It is composed of four func- tional domains: the head piece (HP), core domains 1 and 2 (CD1 and CD2), and the tail piece (TP). The HP is at the N terminus (NT), and it contains four alpha helices (represented by circles 1-4), which function in DNA binding. Together, the core domains contain 12 beta sheets (represented by squares A-L) sandwiched between nine alpha heli- ces (circles 5-13). The tail piece contains an alpha

(Reprinted with permission from M. Lewis et al., 1996, Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271 [5253]: 1247-1254. © 1996 American Association for the Advancement of Science.)

helix (circle 14) near the C terminus (CT) of the protein. The average alpha helix contains 11 amino acids; the average beta sheet, 4 or 5. As shown in diagram B on page 246, the repressor is a V-shaped molecule. Paired dimers make up the arms of the V, but all four chains are bound together at their C termini. The N termini of each dimer bind to differ- ent DNA segments. Inducer molecules can bind to the core in the starred regions. The shape change that follows moves the head piece out of the contact with its binding site on the DNA, and the RNA polymerase can now transcribe the structural genes of the operon.

See Appendix C, 1966, Gilbert and Mu¨ller-Hill; 1996, Lewis et al. lactamase See penicillin. lactic dehydrogenase See isozymes. lactogenic hormone a protein hormone secreted by the anterior lobe of the pituitary that stimulates milk production in mammals and broodiness in birds. See human growth hormone. lactose 4-(β-D-galactoside)-D-glucose. A disaccha- ride made up of two hexoses joined by a beta galac- toside linkage. It is split into galatose and glucose by the enzyme beta galactosidase. Lactose differs from allolactose in that in lactose the galactose and glu- cose moieties are joined by a 1-4 linkage, whereas in allolactose the linkage is 1-6. As its name implies, lactose is abundant in the milk of mammals. See lac operon.

lagging delayed movement from the equator to the poles at anaphase of a chromosome so that it becomes excluded from the daughter nuclei. lagging strand the discontinuously synthesized strand of DNA containing ligated Okazaki fragments (q.v.). See leading strand, replication of DNA. lag growth phase a period of time in the growth of a population during which little or no increase in the number of organisms occurs. The lag period pre- cedes the exponential growth phase (q.v.). lag load a measure of the distance of a species from its local adaptive peak.

The greater the lag load of a species, the more selective pressure is applied to the species, and hence the more rapid the rate of evolution it is likely to be experiencing. Also called evolutionary lag. See Red Queen hypothesis. Lamarckism a historically important, but no longer credited, theory that species can change grad- ually into new species by the willful striving of or- ganisms to meet their own needs, together with the cumulative effects of use and disuse of body parts. All such acquired characteristics were thought to be- come part of the individual’s heredity and as such could be transmitted to their offspring; otherwise known as the inheritance of acquired characteristics. See Appendix C, 1809, Lamarck. lambda ( ) bacteriophage a double-stranded DNA virus that infects E. coli.

The head of the virus con- tains a linear DNA molecule 48,514 bp long. How- ever, upon entering the bacterium, the two ends of the DNA molecule become covalently joined to form a circle. Once inside the host cell, the virus can enter either a lytic developmental cycle or a lyso- genic cycle. Specific repressors control the switch for either cycle. If the lysogenic cycle is chosen, the vi- rus is eventually integrated into the E. coli chromo- some at a specific site. See Appendix C, 1950, Led- erberg; 1961, Meselson and Weigle; 1965, Rothman; 1967, Taylor, Hradecna, and Szybalski; 1968, Davis and Davidson; 1969, Westmoreland et al., 1974, Murray and Murray; Appendix F; cro repressor, lambda cloning vector, lambda repressor, lysogenic cycle, lytic cycle, prophage, site-specific recombina- tion, virus. lambda cloning vector a lambda phage that is ge- netically engineered to serve as a receptor for foreign DNA fragments in recombinant DNA experiments. Vectors that have a single target site at which for-

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