Method of detecting truncated epidermal growth factor receptors

Details Method of detecting truncated epidermal growth factor receptors Method of detecting truncated epidermal growth factor receptors

1985-09-30

1990-06-12

Warden, Robert J.

Chemistry: analytical and immunological testing

Biospecific ligand binding assay

435 4, 435 7, 435 15, 436503, 436518, 436813, 436815, 436817, G01N 3353, G01N 33566, G01N 33543, C12Q 148

Patent

active

049332945

DESCRIPTION:

BRIEF SUMMARY
This invention relates to new polypeptides of interest in the detection of abnormalities in mammalian cell growth and in the control of mammalian cell growth.
Regulation of the proliferation of cells in culture can be influenced by a number of mitogens including a series of polypeptide growth factors which, acting alone or synergistically with other mitogens, can induce DNA synthesis and proliferation of specific target cells. (For recent reviews see ref. 1). Epidermal growth factor (EGF) and platelet derived growth factor (PDGF) are probably the best characterised growth factors, however the precise function of these polypeptides in vivo is unclear. EGF may have a role in cell proliferation and differentiation since it will induce early eyelid opening and incisor development in new born mice (2); PDGF on the other hand, which is released from platelets during blood clot formation at wound sites, may have a role in repair processes (3). These and other growth factors in vitro can trigger a variety of morphological and biochemical changes that resemble those characteristic of transformed cells, and have also been implicated in the abnormal regulation of proliferation shown by transformed and tumour-derived cell lines (reviewed in (4,5)). Thus it has been suggested that transformed cells may both synthesise and respond to growth factors and consequently proliferate independently through `autocrine` secretion (6). Direct support for such an autocrine role for aberrantly expressed growth factors in the control of abnormal cell proliferation came recently from the discovery that the putative transforming protein (p28.sup.sis) of simian sarcoma virus (SSV) is structurally related to the growth factor PDGF (7-9) and can also function like PDGF as a growth factor for cells in culture (10). Other growth factors produced by transformed cells such as insulin-like growth factor (IGF) (11,12), fibroblast derived growth factor (13,14) and the transforming growth factors (TGFs) (15-20), may also act as autocrine regulators of proliferation. Besides the specificity mediated by regulation of the production of growth factors, cellular specificity could also be controlled at several other levels--the most obvious being by binding of ligand to specific receptors present only on target cells. In addition the binding of one growth factor to its specific receptor can also alter the affinity of another growth factor for its receptor (e.g., PDGF and the EGF receptor (21,22)). Conversely two growth factors may, as appears to be the case with .alpha.TGFs and EGF, bind to the same receptor (23,24).
It is clear that binding of different growth factors to their specific receptors can induce a cascade of biochemical events including rapid changes in ion movements and intracellular pH, stimulation of tyrosine specific protein kinases and several other changes which can culminate in DNA synthesis and proliferation of certain target cells (1,4-6). It seems likely that at least in the case of the EGF receptor the primary function of EGF may be to induce cross-linking or conformational changes of receptors, and that following such an activation step, all the `information` necessary for triggering a proliferative response may reside in the receptor itself (see reviews in reference 1). One known function intrinsic to the EGF receptor is its ability to prophorylate tyrosine residues (25-28), a property shared with 5 of the putative transforming proteins of the family of retrovirus whose oncogenes are related to src but not by 2 others, the proteins encoded by mos and erb-B (29). At present this tyrosine kinase activity provides the only functional activity associated with the oncogenes of this subset of retroviruses. None of this family of oncogenes has heretofore been identified as having a cellular homologue that functions as a growth factor receptor.
We have determined the amino acid sequence analysis of 6 distinct peptides from human EGF receptors isolated by monoclonal immunoaffinity purification from A431 cells and placents, and show that

REFERENCES:
Lin, C., et al., Science, 224:843-848 (1984).
Xu, Y. H., et al., Nature, 309:806-810 (1984).
Ullrich, A., et al., Nature, 309:418-425 (1984).
Merlino, G., et al., Science, 224:417-419 (1984).

Affiliated with

Also associated with

Rating

Method of detecting truncated epidermal growth factor receptors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method of detecting truncated epidermal growth factor receptors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of detecting truncated epidermal growth factor receptors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-617012