GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours

Mutations can cause autostimulation of cells, that normally would depend on outside signals, such as hormones, for growth. Abnormal cell growth and tumor development can occur. In patients with acromegaly, enlargement of bones of the face and extremities, mutations have been found in a subset of four human growth hormone-secreting pituitary tumors. These mutations cause autonomous stimulation of cyclic adenosine monophosphate (cAMP, which mediates many signals for cell growth), and result in abnormal secretion of growth hormone and increased cell growth. The mutations occur in a protein which normally binds and breakdowns guanosine triphosphate (GTP, which regulates the stimulation of cAMP). The binding of GTP is inhibited, and cAMP is constantly stimulated. These studies further the understanding of factors that control cell growth the relationship of mutation to abnormal growth or cancer.