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PubMed1994

Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin.

The initiation of maximal DNA synthesis by fibroblast growth factor (FGF)-1 requires the presence of the growth factor during the entire G0 to G1 transition period of the cell cycle (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 9611-9620). During this time, the phosphorylation of several novel proteins on tyrosine residues occurs, and one of these phosphotyrosyl-containing proteins has been characterized as the murine homolog of the chicken cortactin gene (Zhan, X., Hu, X., Hampton, B., Burgess, W.H., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 24427-24431), a putative substrate for v-Src. We have examined the possibility that FGF-1 employs c-Src or Src-like kinases as signaling intermediates during the mid and late G1 phase of the NIH 3T3 cell cycle using immunoprecipitation and immunoblot analysis. We have demonstrated that c-Src can associate with cortactin in a FGF-1-dependent manner. We have also demonstrated that a monoclonal antibody prepared against FGF receptor (R)-1 is able to co-precipitate Src-related proteins in lysates from FGF-1-treated NIH 3T3 cells. Furthermore, a kinase-active form of FGFR-1 expressed in a bacterial system was also able to associate with Src kinases in a manner dependent on the phosphorylation status of the FGFR-1 protein. Lastly, the Src homology (SH)-2 domain of v-Src was able to recognize a recombinant form of FGFR-1. Because (i) the association between FGFR-1 and Src-like kinases exhibits kinetics similar to those observed between the Src kinases and cortactin and (ii) the Src-SH2 domain is likely to be involved in the association with FGFR-1, we propose that the association of c-Src with activated FGF receptors may be responsible for the tyrosine phosphorylation of cortactin during the mid to late G1 phase of the cell cycle.

3T3 Cells↗
PubMed1995

Cocaine-associated myocardial infarction. Mortality and complications. Cocaine-Associated Myocardial Infarction Study Group.

BACKGROUND: The frequency of complications in patients with cocaine-associated myocardial infarction is unknown. This study was performed to determine the short-term morbidity and mortality secondary to cocaine-associated myocardial infarction. METHODS: We performed a retrospective cohort study at 29 hospital centers throughout the United States. Patients with cocaine-associated myocardial infarction that occurred between 1987 and 1993 were identified through record review. The primary outcome measures were in-hospital mortality and the incidence and timing of major cardiovascular complications. RESULTS: Cocaine-associated myocardial infarction was identified 136 times in 130 patients. Patients were generally young (mean age, 38 years), nonwhite (72%), tobacco smokers (91%) with a history of cocaine use in the past 24 hours (88%). The initial electrocardiogram disclosed infarction in 44% and ischemia in an additional 18% of patients. Myocardial infarctions were evenly distributed between anterior (45%) and inferior (44%) and were most often non-Q-wave (61%). Complications occurred 64 times in 49 patients (36%; 95% confidence interval, 28% to 44%), including congestive heart failure in nine patients, ventricular tachycardia in 23 patients, supraventricular tachycardia in six patients, and brady-dysrhythmias in 26 patients. Most patients who had complications (90%) had them within 12 hours of presentation. Acute in-hospital mortality was 0% (95% confidence interval, 0% to 2%). CONCLUSIONS: The mortality of patients hospitalized with cocaine-associated myocardial infarction was low. The majority of complications occurred within 12 hours of presentation.

Adult↗
PubMed1997

Mucosa-associated lymphoid tissue (MALT) in Barrett's esophagus: prospective evaluation and association with gastric MALT, MALT lymphoma, and Helicobacter pylori.

OBJECTIVES: Prospective evaluation of the prevalence of mucosa-associated lymphoid tissue (MALT) within Barrett's esophagus and its association with gastric MALT, gastric MALT lymphoma, and H. pylori infection. METHODS: From Barrett's esophagus patients, a minimum of six gastric biopsies were obtained, in addition to Barrett's surveillance biopsies. Additional gastric biopsies were taken from any ulcer(s), nodule(s), polyp(s), or other lesions. Patients with gastroesophageal reflux symptoms without Barrett's esophagus served as controls. RESULTS: One hundred and thirty-nine Barrett's patients were included in the study. One hundred and twenty-two of these patients had gastric biopsies for gastric MALT and H. pylori determination. H. pylori was noted in the stomach of 48 patients and within Barrett's mucosa in 14. Barrett's MALT was noted in seven cases, gastric MALT in 16, and gastric MALT lymphoma in two. None of the 101 control patients had esophageal MALT. Two of the seven patients with Barrett's MALT had gastric MALT. Barrett's MALT was associated with esophageal H. pylori in 57.1% cases and gastric H. pylori in 71.4%. The prevalence of gastric and esophageal H. pylori in patients with Barrett's MALT was significantly higher compared to patients with Barrett's without MALT (p < 0.0001 and p < 0.007, respectively). Barrett's MALT was very focal and its esophageal location variable. CONCLUSIONS: Barrett's MALT was associated with both esophageal and gastric H. pylori colonization. Esophageal MALT was associated with Barrett's esophagus. Gastric biopsy sampling is warranted in any patient with Barrett's MALT to detect gastric MALT and H. pylori, which, if found, should be eradicated.

Adult↗
PubMed2004

Reducing the influence of extrapersonal associations on the Implicit Association Test: personalizing the IAT.

The authors argue that the Implicit Association Test (IAT; A.G. Greenwald, D.E. McGhee, & J.L.K. Schwartz, 1998) can be contaminated by associations that do not contribute to one's evaluation of an attitude object and thus do not become activated when one encounters the object but that are nevertheless available in memory. The authors propose a variant of the IAT that reduces the contamination of these "extrapersonal associations." Consistent with the notion that the traditional version of the IAT is affected by society's negative portrayal of minority groups, the "personalized" IAT revealed relatively less racial prejudice among Whites in Experiments 1 and 2. In Experiments 3 and 4, the personalized IAT correlated more strongly with explicit measures of attitudes and behavioral intentions than did the traditional IAT. The feasibility of disentangling personal and extrapersonal associations is discussed.

Adult↗
PubMed1991

Antibodies to myelin-associated glycoprotein are found in cerebrospinal fluid in polyneuropathy associated with monoclonal serum IgM.

Antibodies to myelin-associated glycoprotein (MAG) have been demonstrated in the serum samples from about half the patients with polyneuropathy associated with serum IgM monoclonal component. We examined cerebrospinal fluid (CSF) and serum samples from 13 patients with this disease by enzyme-linked immunosorbent assay for anti-MAG IgM antibodies. We detected these antibodies in both CSF and serum samples in 10 of the patients; in three of them the antibodies were at higher levels in the CSF. The remaining three patients had anti-MAG IgM antibodies in the CSF only. Intrathecal production of anti-MAG IgM antibodies is thus common in polyneuropathy associated with IgM monoclonal component. In three patients, examined on two occasions from 1 to 7 years, high anti-MAG IgM antibody levels persisted in CSF and serum samples. Among 165 patients with other neurologic diseases, including 60 with multiple sclerosis and 60 control subjects with tension headache, anti-MAG IgM antibodies were detected in the CSF from three patients (two with multiple sclerosis, one with aseptic meningitis), and in the serum sample of one patient with multiple sclerosis. Whether the frequent occurrence of anti-MAG IgM antibodies in CSF and their intrathecal synthesis has pathogenetic relevance for the development of polyneuropathy associated with IgM monoclonal component is unsure.

Aged↗
PubMed1996

Neuropathy associated with "benign" anti-myelin-associated glycoprotein IgM gammopathy: clinical, immunological, neurophysiological pathological findings and response to treatment in 33 cases.

We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46-81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG.

Aged↗
PubMed2005

Mannan-binding-lectin-associated serine proteases, characteristics and disease associations.

Mannan-binding lectin (MBL)-associated serine proteases (MASPs) circulate in plasma as zymogens in complexes with MBL and with L- and H-ficolin. Upon binding of MBL or ficolin to pathogen-associated molecular patterns, the MASPs are activated. MASP-2 can now cleave C4 and C2 to generate the C3 convertase, C4bC2b. The functions of the other two MASPs, MASP-1 and MASP-3 have not been elucidated. MASP-1 can cleave C2, and with low efficiency also C3, and may serve a function through direct C3 activation. No natural substrate for MASP-3 has been identified. MBL deficiency, occurring at a frequency of about 10%, is the most common congenital immunodeficiency and is associated with susceptibility to infections and autoimmune disorders. Inherited MASP-2 deficiency has been described as the result of a mutation causing the exchange of aspartic acid with a glycine at position 105, a position in the first domain, CUB1, involved in calcium binding. This mutation abolishes the binding to MBL and ficolins, and deprives MASP-2 of functional activity. The index case suffered from recurrent severe infections and autoimmune reactions. The gene frequency of the mutation among Caucasians is 3.6%. It is not found in Chinese, who present a different mutation also associated with MASP-2 deficiency.

Amino Acid Sequence↗
PubMed1985

Association states of tubulin in the presence and absence of microtubule-associated proteins. Analysis by electric birefringence.

Electric birefringence has been used to examine the states of association of tubulin in phosphocellulose-purified tubulin or depolymerized microtubule protein solutions at low temperature. In a high electric field (1000-4000 V/cm), tubulin could be orientated (owing to the existence of a permanent and/or induced dipole) and exhibited a positive birefringence (delta n), related to its intrinsic optical anisotropy. The analysis of the relaxation process (depending on hydrodynamic properties of molecules), by measurement of the time decay of delta n, revealed the existence of a multicomponent or polydisperse system, whatever the tubulin solution. Two relaxation times, representative of the smallest and the largest orientated species, were obtained by computer-fitting analysis. The mean values of relaxation time for phosphocellulose-purified tubulin were 0.8 and 8 microseconds. In microtubule protein solutions, large-sized macromolecular species with relaxation time up to 450 microseconds were detected. The largest species (relaxation times ranging from 50 to 450 microseconds) could be eliminated by centrifugation at 3000000 X g for 1 h. Addition of microtubule-associated protein to either pure tubulin or high-speed centrifuged microtubule protein led to a rapid formation of large species analogous to those present in microtubule protein. Molecular dimensions of the relaxing structures were estimated using simple hydrodynamic models and values of rotational diffusion constants calculated from the relaxation times, and compared to those of the structures described in the literature. In conclusion, we have found that (a) phosphocellulose-purified tubulin is not only composed of elementary species (dimers) but also contains tubulin-associated forms of limited size (up to 7-10 dimers), (b) depolymerized microtubule protein solutions contain ring oligomers and structures very much larger, the formation of which is dependent on the presence of microtubule-associated protein.

Animals↗
PubMed2004

Association of GRIP1 with a GABA(A) receptor associated protein suggests a role for GRIP1 at inhibitory synapses.

GABA(A) receptors mediate the majority of fast synaptic inhibition in the mammalian central nervous system. GABA(A) receptors associate with a number of cytosolic proteins important for regulating their function including the GABA(A) receptor gamma2 subunit associated protein GABARAP. Here we show GABARAP associates with the synaptic PDZ domain containing protein GRIP1. GRIP1 has been localized to inhibitory synapses however the role of this protein with respect to neuronal inhibition remains unclear. Using in vitro protein interaction assays we show that GABARAP interacts directly with PDZ domains 4-6 of GRIP1. Furthermore, using coimmunoprecipitation assays we show that GABARAP interacts with GRIP1 in vivo. Finally, we show that GRIP1 colocalizes with gamma2 subunit containing GABA(A) receptors in cultured hippocampal neurons. Our findings provide evidence that GRIP1 can associate with proteins important for regulating GABA(A) receptor function and suggest that GRIP1 may play a role at inhibitory synapses.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population.

Results of gene expression microarray and quantitative PCR studies have suggested abnormalities in the expression of myelin-related genes including myelin-associated glycoprotein (MAG) in schizophrenic patients. Research provides strong evidence for oligodendrocyte dysfunction in schizophrenics. In order to further assess the role of MAG in schizophrenia, we examined four single nucleotide polymorphisms (SNPs), namely rs2301600, rs3746248, rs720309 and rs720308, of this gene in Chinese schizophrenic patients (n=470) and healthy controls (n=470). The distribution of rs720309 T/A genotypes showed a strong association with schizophrenia (chi(2)=14.58, d.f.=2, P=0.0008). A haplotype constructed of rs720309-rs720308 also revealed a significant association with schizophrenia (chi(2)=11.914, d.f.=3, P=0.0084). Our findings of a significant associations between schizophrenia and the MAG gene suggest that this gene may be involved in susceptibility to schizophrenia in the Chinese Han population.

Adult↗
PubMed2005

Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity.

Understanding cognitive aging is becoming more important as the elderly population grows. Here, the effects of age and sex on learning and memory performance were compared in female and male young (3-4 months old) middle-aged (10-12 months old) and old (18-20 months old) wild-type C57BL/6J mice. Old males and females performed worse than young or middle-aged mice in novel location, but not novel object recognition tasks. Old mice, of both sexes, also showed impaired spatial water maze performance during training compared with young or middle-aged mice, however only old females failed to show robust spatial bias during probe trials. While there was no age-difference in passive avoidance performance for males, females showed an age-related decline. There was no difference in cognitive performance between young and middle-age mice of either sex on any task. Cognitive performance was associated with alterations in immunoreactivity of microtubule-associated protein 2-positive dendrites and synaptophysin-positive pre-synaptic terminals in hippocampal CA1, CA3, and dentate, entorhinal cortex, and central nucleus of amygdala. Overall, microtubule-associated protein 2 immunoreactivity was increased in old females compared with both young and middle-age females with no significant difference in males. In contrast, synaptophysin immunoreactivity increased from young to middle-age in females, and from middle-age to old in males; females had higher levels of synaptophysin immunoreactivity than males in middle-age only. Elevated levels of microtubule-associated protein 2 and synaptophysin may constitute a compensatory response to age-related functional decline in mice.

Adaptation, Physiological↗
PubMed1997

The natural resistance-associated macrophage protein gene is associated with Crohn's disease.

BACKGROUND: Identification of the genes causing inflammatory bowel disease (IBD) would enhance the understanding of and the treatment options for this disease. A hyperreactive immune response toward the intestinal flora has been implicated in the pathology of IBD. The natural resistance-associated macrophage protein (NRAMP) gene is believed to regulate macrophage function, especially the ability to fight intracellular pathogens. Genetic differences of NRAMP might, therefore, be associated with IBD. METHODS: Two DNA markers (D2S434 and D2S1323) near NRAMP were polymerase chain reaction (PCR) amplified and genotyped with DNA from 103 patients with Crohn's disease, 85 patients with ulcerative colitis, and 98 control subjects. Clinical data were obtained for all patients. Comparisons were made by chi-squared analysis. Disease association with significant haplotypes was expressed as odds ratio. RESULTS: Allele and genotype distributions were similar for both markers among all groups. Haplotype frequencies were different among Crohn's disease and control groups (p = 0.024). Two individual haplotypes of the patients with Crohn's disease were significant compared with control subjects: DA (p = 0.023; odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9) and EA (p = 0.001; odds ratio, 3.5; 95% confidence interval, 1.6 to 3.2). The haplotype distribution was different within three age-of-onset groups of patients with Crohn's disease (p = 0.05). CONCLUSIONS: This study is the first to report an association between the NRAMP gene and Crohn's disease.

Adolescent↗
PubMed2004

Underlying processes in the implicit association test: dissociating salience from associations.

The authors investigated whether effects of the Implicit Association Test (IAT) are influenced by salience asymmetries, independent of associations. Two series of experiments analyzed unique effects of salience by using nonassociated, neutral categories that differed in salience. In a 3rd series, salience asymmetries were manipulated experimentally while holding associations between categories constant. In a 4th series, valent associations of the target categories were manipulated experimentally while holding salience asymmetries constant. Throughout, IAT effects were found to depend on salience asymmetries. Additionally, salience asymmetries between categories were assessed directly with a visual search task to provide an independent criterion of salience asymmetries. Salience asymmetries corresponded to IAT effects and also accounted for common variance in IAT effects and explicit measures of attitudes or the self-concept.

Adult↗
PubMed2006

The association between psychological distance and construal level: evidence from an implicit association test.

According to construal level theory (N. Liberman, Y. Trope, & E. Stephan, in press; Y. Trope & N. Liberman, 2003), people use a more abstract, high construal level when judging, perceiving, and predicting more psychologically distal targets, and they judge more abstract targets as being more psychologically distal. The present research demonstrated that associations between more distance and higher level of construal also exist on a pure conceptual level. Eight experiments used the Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K. Schwartz, 1998) to demonstrate an association between words related to construal level (low vs. high) and words related to four dimensions of distance (proximal vs. distal): temporal distance, spatial distance, social distance, and hypotheticality. In addition to demonstrating an association between level of construal and psychological distance, these findings also corroborate the assumption that all 4 dimensions of psychological distance are related to level of construal in a similar way and support the notion that they all are forms of psychological distance.

Concept Formation↗
PubMed2003

Degraded myelin-associated glycoprotein (dMAG) formation from pure human brain myelin-associated glycoprotein (MAG) is not mediated by calpain or cathepsin L-like activities.

The myelin-associated glycoprotein (MAG) is a transmembrane cell adhesion molecule participating in myelin formation and maintenance. Calcium-activated/-dependent proteolysis of myelin-associated glycoprotein by calpain and cathepsin L-like activities has already been detected in purified myelin fractions, producing a soluble fragment, called degraded (d)MAG, characterized by the loss of the transmembrane and cytoplasmic domains. Here, we demonstrate and analyze dMAG formation from pure human brain myelin-associated glycoprotein. The activity never exhibited the high rate previously reported in human myelin fractions. Degradation is time-, temperature-, buffer- and structure-dependent, is inhibited at 4 degrees C and by denaturation of the sample, and is mediated by a trans-acting factor. There is no strict pH dependency of the proteolysis. Degradation was inhibited by excess aprotinin, but not by 1-10 micro g/mL aprotinin and was not eliminated by the use of an aprotinin-sepharose matrix during the purification. dMAG formation was not enhanced by calcium, nor inhibited by a wide variety of protease inhibitors, including specific calpain and cathepsin L inhibitors. Therefore, while cysteine proteases may be present in human myelin membrane fractions, they are not involved in dMAG formation from highly purified human brain myelin-associated glycoprotein preparations.

Aged↗
PubMed2002

Gamma interferon and granulocyte/monocyte colony-stimulating factor prevent endotoxin tolerance in human monocytes by promoting interleukin-1 receptor-associated kinase expression and its association to MyD88 and not by modulating TLR4 expression.

Endotoxin tolerance is characterized by a decreased production of proinflammatory cytokines by cultured leukocytes in response to lipopolysaccharide (LPS) following a first exposure to the same stimulus. Gamma interferon (IFNgamma) and granulocyte/monocyte colony-stimulating factor (GM-CSF) are immunostimulatory cytokines that prime monocytes and prevent endotoxin tolerance. In this study, we show that the deactivating effects of LPS, as well as the priming effects of IFNgamma and GM-CSF or their capacity to restore tumor necrosis factor (TNF) production by LPS-tolerized human monocytes are independent of the modulation of TLR2, TLR4, or MD-2. In monocytes pretreated with IFNgamma or GM-CSF, interleukin-1 receptor-associated kinase (IRAK) expression is up-regulated. After LPS stimulation, an increased IRAK kinase activity, a higher MyD88/IRAK association, and a stronger NF-kappaB activation are observed. In contrast, in LPS-tolerized monocytes, IRAK expression and kinase activity, IRAK/MyD88 association, and NF-kappaB activation are inhibited. Furthermore, the prevention of tolerance by IFNgamma and GM-CSF was independent of IRAK kinase activity. Our results suggest that these cytokines prevent endotoxin tolerance induced by low but not by high doses of LPS by inhibiting IRAK degradation and by promoting its association with MyD88 after a second LPS stimulation, which in turn leads to NF-kappaB activation and TNF production.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Gram-negative flagellin-induced self-tolerance is associated with a block in interleukin-1 receptor-associated kinase release from toll-like receptor 5.

Flagellin from a number of Gram-negative bacteria induces cytokine and nitric oxide production by inflammatory cell types. In view of the evidence that flagellin responsiveness is subject to modulation, we explored the possibilities that a prior exposure to flagellin might result in a state of reduced flagellin responsiveness or tolerance and that lipopolysaccharide (LPS) and flagellin may induce a state of cross-tolerance to each other. Our results demonstrate that a prior exposure to flagellin results in a subsequent state of flagellin tolerance in human monocytes, THP1 cells, Jurkat cells, and COS-1 cells. Tolerance occurs within 2 h after addition of flagellin and does not require protein synthesis. Flagellin did not induce tolerance to LPS in monocytes and THP1 cells; however, LPS treatment of monocytes and THP1 cells resulted in a state of flagellin cross-tolerance. Flagellin-induced self-tolerance is not the result of a decrease in the steady-state level of toll-like receptor 5 (TLR5) or interleukin-1 receptor associated kinase (IRAK), but it is associated with a block in the release of IRAK from the TLR5 complex in flagellin-tolerant cells. Release is essential for IRAK activity because the TLR5-associated IRAK lacks kinase activity. LPS-induced cross-tolerance to flagellin is also associated with a block in IRAK release from TLR5. These results provide evidence for a novel mechanism of TLR signaling control.

Animals↗
PubMed2006

Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2.

The microtubule-associated protein (MAP)/microtubule affinity regulating kinase (MARK)/Par-1 phosphorylates microtubule-associated proteins tau, MAP2, and MAP4 and is involved in the regulation of microtubule-based transport. Par-1, a homologue of MARK in Drosophila and Caenorhabditis elegans, is essential for the development of embryonic polarity. Four isoforms of MARK are found in humans. Recently, we reported the crystal structure of the catalytic and ubiquitin-associated domains of MARK2, an isoform enriched in brain (Panneerselvam, S., Marx, A., Mandelkow, E.-M., and Mandelkow, E. (2006) Structure 14, 173-183). It showed that the ubiquitin-associated domain (UBA) domain has an unusual fold and binds to the N-terminal lobe of the catalytic domain. This is at variance with a previous low resolution structure derived from small angle solution scattering (Jaleel, M., Villa, F., Deak, M., Toth, R., Prescott, A. R., Van Aalten, D. M., and Alessi, D. R. (2006) Biochem. J. 394, 545-555), which predicts binding of the UBA domain to the larger, C-terminal lobe. Here we report the crystal structure of the catalytic and UBA domain of another isoform, MARK1. Although the crystal packing of the two isoforms are unrelated, the overall conformations of the molecules are similar. Notably, the UBA domain has the same unusual conformation as in MARK2, and it binds at the same site. Remarkable differences occur in the catalytic domain at helix C, the catalytic loop, and the activation segment.

Amino Acid Sequence↗