IDENTIFICATION OF 2 JUXTAMEMBRANE AUTOPHOSPHORYLATION SITES IN THE PDGF BETA-RECEPTOR - INVOLVEMENT IN THE INTERACTION WITH SRC FAMILY TYROSINE KINASES

被引:330
|
作者
MORI, S
RONNSTRAND, L
YOKOTE, K
ENGSTROM, A
COURTNEIDGE, SA
CLAESSONWELSH, L
HELDIN, CH
机构
[1] BIOMED CTR,LUDWIG INST CANC RES,BOX 595,S-75124 UPPSALA,SWEDEN
[2] BIOMED CTR,DEPT IMMUNOL,S-75123 UPPSALA,SWEDEN
[3] EUROPEAN MOLEC BIOL LAB,DIFFERENTIAT PROGRAMME,W-6900 HEIDELBERG,GERMANY
来源
EMBO JOURNAL | 1993年 / 12卷 / 06期
关键词
AUTOPHOSPHORYLATION; PDGF BETA-RECEPTOR; SRC FAMILY TYROSINE KINASES; SRC HOMOLOGY-2 DOMAIN; TYROSINE PHOSPHORYLATION;
D O I
10.1002/j.1460-2075.1993.tb05879.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Two novel sites of autophosphorylation were localized to the juxtamembrane segment of the human platelet-derived growth factor (PDGF) beta-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants were made in which Tyr579, Tyr581 or both were replaced with phenylalanine residues; the receptor mutants were stably expressed in porcine aortic endothelial cells. Compared with the wild-type receptor, the Y579F and Y581F mutants were less able to mediate association with and activation of the Src family tyrosine kinases. The ability of these phosphorylation sites to mediate directly the binding of the Src family proteins was also demonstrated by using phosphotyrosine-containing synthetic peptides representing the juxtamembrane sequence of the receptor. Both the Y579F and Y581F mutants were similar to the wild-type receptor with regard to their protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. A conclusive evaluation of the role of the Src family members in signal transduction could, however, not be made since our attempt to prevent completely the association by mutation of both Tyr579 and Tyr581, resulted in loss of kinase activity and was therefore not informative. The present data, together with previous observations, demonstrate a high degree of specificity in the interaction between different autophosphorylation sites in the PDGF beta-receptor and downstream components in the signal transduction pathway.
引用
收藏
页码:2257 / 2264
页数:8
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