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Differential heat stress stability of epidermal growth factor receptor and erb B‐2 receptor tyrosine kinase activities
Author(s) -
Liu Samuel M.,
Carpenter Graham
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041570205
Subject(s) - autophosphorylation , tropomyosin receptor kinase c , tyrosine kinase , receptor tyrosine kinase , epidermal growth factor , erbb , ror1 , biology , growth factor receptor , platelet derived growth factor receptor , microbiology and biotechnology , receptor , chemistry , biochemistry , signal transduction , kinase , protein kinase a , growth factor
The epidermal growth factor (EGF) and erb B‐2 receptors are structurally related membrane‐bound tyrosine kinases. While these proteins exhibit close sequence homology, 50% overall and 80% in the tyrosine kinase domains, they respond very differently to heat stress. In NIH‐3T3 or NR6 cells transfected with wild‐type EGF‐R and incubated at 37°C or heat shocked at 46°C, EGF binds to its receptor and stimulates receptor autophosphorylation to equivalent extents. At 46°C, however, the basal tyrosine kinase activity of the wild‐type erb B‐2 receptor is rapidly lost. When cells containing chimeric receptors composed of the EGF‐R extracellular domain and intracellular domain of erb B‐2 were heat stressed, 125 I‐EGF bound to the receptors, but did not stimulate receptor autophosphorylation. The decline in EGF‐stimulated chimeric erb B‐2 receptor autophosphorylation is dependent on the length of heat shock, with nearly 100% of the kinase activity lost after 60 min at 46°C. The loss of chimeric receptor erb B‐2 kinase activity is not due to degradation of receptor protein, nor is it attributable to a specific transmembrane domain from either the EGF or erb B‐2 receptors. Sensitivity of erb B‐2 to heat stress is also not a result of denaturation of this receptor's carboxy‐terminal domain. Insertion of the erb B‐2 tyrosine kinase domain into the EGF‐R confers heat stress sensitivity to the resultant chimeric receptor. Thus, although the EGF‐R and erb B‐2 kinase domains show a high degree of homology, the secondary/tertiary structures of these domains would seem to be stabilized in distinct manners. © 1993 Wiley‐Liss, Inc.