102,295 research outputs found
The impairment of auditory-verbal short-term storage
No full textThis work summarizes the empirical and theoretical work on impairments of short-term memory (often caused by damage in the left cerebral hemisphere) and contains chapters from virtually every scientist in Europe and North America working on the problem. The chapters present evidence from both normal and brain-damaged patients. Two neuropsychological issues are discussed in detail: first, the specific patterns of immediate memory impairment resulting from brain damage with reference to both multistore and the interactive-activation theoretical frameworks. Also considered is the relation between verbal STM and sentence comprehension disorders in patients with a defective immediate auditory memory: an area of major controversy in more recent years
G protein oncogenes in pituitary tumors
No full textG proteins are involved in the transduction of external signals from cell surface receptors to intracellular effectors. Somatic mutations activating the a-subunit of Gs (the stimulatory regulatory protein of adenylyl cyclase) by inhibiting its intrinsic GTPase activity have been first identified in human GH-secreting adenomas and subsequently found in thyroid tumors and in McCune-Albright syndrome. It has been therefore proposed that the gene encoding the GS a-subunit may be converted into an oncogene (gsp for GS protein) in cell types that proliferate in response to cAMP. Since several G proteins mediate signaling pathways that are effective in coupling external stimuli to cell proliferation, it appears most likely that in the near future other G protein oncogenes will be identified in human tumors
Oncogenic role of heterotrimeric G proteins
No full textMutations that constitutively activate the α chains of G(s) and G(i2) by inhibiting their intrinsic GTPase activity are present in human endocrine tumours. The gsp oncogene is mainly found in pituitary GH secreting tumours and thyroid hyperfunctioning adenomas, where it induces a constitutive activation of the adenylyl cyclase-cAMP pathway. In pituitary and thyroid cells, this signal leads to abnormal proliferation and a persistent activation of differentiated functions. The gip2 oncogene has been identified in tumours of the ovary and adrenal cortex. Although the mechanisms of the oncogenic action of mutationally activated α(i2) are less clear than those of α(s), the protein can induce transformation of certain cell types. At least five other α chains, which share with α(s) and α(i2) common structural and functional mechanisms of GTP hydrolysis, activate mitogenic pathways leading to transformation. In addition, the G protein βγ subunits clearly control signals involved in cell growth. So far, there is no evidence for mutations of these molecules in human tumours. Further studies will tell us whether at present we know of only two members of a much larger family of G protein oncogenes
G protein oncogenes in acromegaly
No full textG-proteins belong to a family of proteins which share the common properties of GTP binding and hydrolysis. Heterotrimeric G-proteins are composed of α-, β- and γ-subunits. The α-subunit which differs from one G-protein to another contains the GDP/GTP binding site and has intrinsic GTPase activity. The receptor occupancy causes displacement of bound GDP by GTP, dissociation of free βγ-dimer and α-GTP complex, interaction of the activated α-GTP complex with intraceilular effectors, such as enzymes and ion channels. The turn off of the reaction is due to the GTPase activity which causes the hydrolysis of GTP to GDP. G-proteins are essential for transferring hormonal signals from cell surface receptors to intracellular effectors. Since G-proteins generate intracellular effectors involved in cell growth, G-protein genes have the propensity to be converted into oncogenes. In fact, mutations in the α-subunit of Gs (the G-protein involved in the activation of adenylyl cyclase) have been demonstrated in 40% of human GH secreting pituitary adenomas. Single amino acid substitutions replacing Arg 201 with either Cys or His or Gln 227 with either Arg or Leu cause constitutive activation of adenylyl cyclase by inhibiting GTPase (gsp oncogene). The same mutations were identified in about 10% of thyroid adenomas and in the McCune-Albright syndrome
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