Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple endocrine neoplasia (MEN) type 2A (MEN 2A) and type 2B (MEN 2B) are dominantly inherited with a predisposition to endocrine tumors. The responsible genes for MEN 2A and 2B have recently been localized to chromosome 10q 11.2 by genetic and physical mapping. The DNA segment encompasses the RET proto-oncogene. This is a receptor tyrosine kinase gene, which is expressed in medullary thyroid carcinoma and pheochromocytoma. Point mutations in the cysteine-rich domain of the RET were demonstrated in patients with MEN 2A. The cosegregation of these mutations and disease in MEN 2A families indicates that they possess a predisposition endocrine organs to develop into tumors. Biological assessment of the mutant forms in cell culture and transgenic mouse lines should provide further insight as to the role of the RET in the tumor development.
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PMID:[The molecular genetics of multiple endocrine neoplasia type 2A and 2B]. 791 Aug 61

Patients with MEN 2A, MEN 2B, and familial non-MEN medullary thyroid carcinoma (MTC) inherit MTC in an autosomal dominant fashion. This malignancy has been diagnosed previously by detecting elevated plasma calcitonin levels, a tumor marker for MTC, following the intravenous administration of secretagogues. Although the study of large pedigrees with MEN 2A, using highly informative flanking markers and linkage analysis, are highly accurate in predicting the inheritance of the disease, the method is indirect and somewhat cumbersome. Mutations in the RET proto-oncogene have been identified independently in patients with MEN 2A and familial medullary thyroid carcinoma. Even though the RET mutations are inherited with disease, there is no direct evidence that the mutations cause the MEN 2 syndromes. The usefulness of molecular methods in the diagnosis and treatment of patients with these syndromes is discussed, and a strategy for deciding operative intervention is presented.
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PMID:Current perspectives on the diagnosis and management of patients with multiple endocrine neoplasia type 2 syndromes. 791 27

The occurrence of mutations in the RET protooncogene has been investigated in 12 multiple endocrine neoplasia type 2A families and 18 cases of sporadic thyroid medullary carcinomas and pheochromocytomas. Ten of 12 families showed single base substitutions in the RET protooncogene exons 10 and 11, coding for the extracellular domain of the protein. Tumor tissues from 2 multiple endocrine neoplasia type 2A patients were analyzed at the DNA and ribonucleic acid levels and revealed the same heterozygous mutations found in the peripheral blood lymphocytes. This demonstrates that both the normal and mutant alleles are expressed. No mutations in these exons were detected in the 18 cases of sporadic tumors investigated. These data provided further evidence that the mutated RET protooncogene acts in a dominant fashion and is responsible for the pathogenesis of this syndrome.
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PMID:Frequent RET protooncogene mutations in multiple endocrine neoplasia type 2A. 791 36

Following the recent identification of specific germline mutations of the RET proto-oncogene in Multiple Endocrine Neoplasia type 2A (MEN2A) patients, we looked for mutations of this gene in a pedigree showing recurrence of MEN2A and localized Cutaneous Lichen Amyloidosis (CLA). Basal calcitonin and/or pentagastrin test performed in all the 10 available members of this pedigree confirmed the clinical diagnosis and allowed the presymptomatic identification of an additional carrier. A cys634-->tyr missense mutation, already reported as causative in MEN2A patients, was identified after SSCP analysis and direct sequencing of exon 11 of the RET protooncogene in one individual affected with both MEN2A and CLA, thus suggesting a common etiology for the two disorders. Taking advantage of the observation of an RsaI restriction site in the sequence surrounding the mutated codon, we could demonstrate that the same mutation is present in three other affected members, in the presymptomatic carrier and in one additional 25 years old healthy member who shows a mildly positive pentagastrin test.
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PMID:Identification of the Cys634-->Tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis. 791 13

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are two closely related cancer syndromes inherited in an autosomal dominant manner. Mutations in the RET proto-oncogene were found in MEN 2A and FMTC families. In this study we report seven different germline mutations in the RET proto-oncogene in five of five MEN 2A and five of six FMTC families. Each of the mutations involves a cysteine residue in the extracellular cysteine-rich domain of the RET receptor tyrosine kinase. We developed simple polymerase chain reaction based diagnostic tests for all seven mutations in these families.
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PMID:Germline RET mutations in MEN 2A and FMTC and their detection by simple DNA diagnostic tests. 791 65

Mutations in the RET proto-oncogene have been identified in the constitutional DNA of patients with the inherited disorders multiple endocrine neoplasia type 2A and 2B and familial medullary thyroid carcinoma. This review focuses on the discoveries over the past year that pointed to RET as a candidate gene, and on the nature and spectrum of what appear to be dominant mutations associated with an inherited predisposition to tumor development.
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PMID:Inherited cancers associated with the RET proto-oncogene. 791 23

We have previously reported that fetal and adult skin fibroblasts display distinctive migratory phenotypes on 3-D collagen substrata and that these behavioural characteristics may be quantified by a function defined as the cell density migration index (CDMI). Subsequent work indicated that this difference in migratory phenotype was due to the production by fetal fibroblasts of a migration stimulating factor (MSF) that is not produced by normal adult skin fibroblasts. We now present data indicating that: (a) unselected fibroblasts obtained from 14/14 (100%) of adult gingival explants expressed fetal-like CDMI values compared to only 1/10 (10%) of similarly explanted paired skin cells; (b) 12/12 (100%) of these gingival fibroblast lines also produced detectable quantities of MSF compared to 0/9 (0%) of the tested skin cells; (c) by microdissection studies, gingival fibroblasts obtained from different anatomical microdomains consisted of behaviourally distinct subpopulations, with cells derived from the papillary tips (PAP fibroblasts) displaying fetal-like CDMI values and persistent MSF production, whilst cells obtained from the deeper reticular tissue (RET fibroblasts) were adult-like with respect to these two criteria; (d) PAP fibroblasts were also smaller and achieved higher saturation cell densities compared to paired RET cells; (e) PAP fibroblasts passaged in vitro underwent a fetal-to-adult phenotypic transition characterized by the adoption of various RET cell characteristics, including the acquisition of CDMI values falling within the adult range and cessation in MSF production; and (f) early passage PAP fibroblasts incubated in the presence of an affinity-purified anti-MSF rabbit polyclonal antibody were induced to alter their migratory phenotype and exhibited CDMI values falling within the adult range. Statistical analysis indicated a highly significant correlation between the expression of a fetal-like CDMI and production of MSF (P < 0.00001, using the Fisher exact contingency test). Taken together, these observations suggest that the production of MSF by PAP fibroblasts is responsible for their characteristically fetal-like migratory behaviour. The existence of such inter- and intra-site phenotypic heterogeneity in populations of skin and gingival fibroblasts is discussed in the context of fibroblast lineage relationships and the possible contribution of persistently fetal-like fibroblast subpopulations to connective tissue function in wound healing.
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PMID:Inter- and intra-site heterogeneity in the expression of fetal-like phenotypic characteristics by gingival fibroblasts: potential significance for wound healing. 792 39

To summarise then, in 1962 RET displayed important features still current. These include the interrelatedness of cognitive, emotive and behavioural processes, the important role that cognition plays in psychological problems, its humanistic view of the self, and the futility and dangers of self-rating. The emphasis on perpetuation rather than acquisition processes of emotional disturbance holds good now as it did then, and the core view of therapeutic change is essentially the same now as it was in 1962, despite further, more recent elaborations. Significant change has occurred in RET since 1962 that updates several of Ellis' original ideas. These include the distinction between interpretations (or inferences) and evaluations, the primary of musts in accounting for psychological disturbance, the clear distinction between healthy and unhealthy negative emotions and the greater role according to force and energy in the change process. In addition, a greater emphasis is placed on biological aspects of emotional disturbance now than 30 years ago. Finally, a greater range of cognitive, imaginal, emotive and behavioural methods are found in current RET literature than in Reason and Emotion in Psychotherapy, where Ellis restricts himself to illustrating a few cognitive and behavioural techniques. RET, then, has grown and developed over the past 30 years. In large part, this reflects the theory's flexibility and the competent people who have worked to make RET one of the most viable and widely used cognitive-behaviour therapies.
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PMID:Reason and emotion in psychotherapy: Albert Ellis. 795 24

Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line DNA of MEN 2B patients. We have analyzed 25 cases of de novo disease in order to determine the parental origin of the mutated RET allele. In all cases the new mutation was of paternal origin. We observe a distortion of the sex ratio in both de novo MEN 2B patients and the affected offspring of MEN 2B transmitting males. These results suggests a differential susceptibility of RET to mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development.
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PMID:Parent-of-origin effects in multiple endocrine neoplasia type 2B. 797 64

Hirschsprung's disease (HSCR) is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates and megacolon in infants and adults. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR. Recently, a gene for HSCR has been mapped to chromosome 10q11.2. No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest. Here we report on nonsense and missense mutations in the extracellular domain of the RET protein (exons 2, 3, 5 and 6) in 6 unrelated probands and show that the mutant genotypes segregate with the disease in HSCR families. Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A). Thus, germ-line mutations of the RET gene may contribute either to developmental anomalies in HSCR or to inherited predisposition to cancer in MEN 2A.
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PMID:[Mutations of RET proto-oncogene in Hirschsprung disease]. 800 Sep 15


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