ERBB2 KD mutants heterodimerize

The following ERBB2 KD mutants were directly or indirectly shown to form heterodimers with EGFR:<br><br>ERBB2 L755P (Kancha et al. 2011 – indirect, higher catalytic activity in the presence of EGF stimulated EGFR);<br>ERBB2 L755S (Kancha et al. 2011, Bose et al. 2013 – indirect, higher kinase activity in the presence of EGFR);<br>ERBB2 I767M (Bose et al. 2013 – indirect, EGFR is phosphorylated in the presence of ERBB2 I767M);<br>ERBB2 D769H (Bose et al. 2013 – indirect, trans autophosphorylation in the presence of EGFR);<br>ERBB2 D769Y (Bose et al. 2013 – indirect, trans autophosphorylation in the presence of EGFR);<br>ERBB2 V777L (Kancha et al. 2011, Bose et al. 2013 – indirect, increased catalytic activity in the presence of EGF activated EGFR);<br>ERBB2 G778_P780dup (Bose et al. 2013, Suzawa et al. 2016, Ogoshi et al. 2019 – indirect, trans-autophosphorylates in the presence of EGFR);<br>ERBB2 T798M (Kancha et al. 2011, Rexer et al. 2013 – indirect, trans-autophosphorylation in the presence of EGF-stimulated EGFR);<br>ERBB2 V842I (Bose et al. 2013 – indirect, trans-autophosphorylation in the presence of EGFR);<br>ERBB2 T862A (Kancha et al. 2011 –indirect, increased catalytic activity in the presence of EGF activated EGFR);<br>ERBB2 H878Y (Kancha et al. 2011 – indirect, activated in the presence of EGF-stimulated EGFR);<br>ERBB2 R896C (Bose et al. 2013 – indirect, trans autophosphorylation in the presence of EGFR);<br>ERBB2 L755_T759del (Bose et al. 2013 – indirect, EGFR phosphorylated in the presence of the mutant);<br>ERBB2 Y772_A775dup (Wang et al. 2006 - direct)<br><br>The following ERBB2 KD mutants were directly or indirectly shown to form heterodimers with ERBB3:<br><br>ERBB2 L755P (Kancha et al. 2011 – indirect, higher catalytic activity in the presence of neuregulin stimulated ERBB3);<br>ERBB2 L755S (Croessmann et al. 2019 – direct, mutant forms heterodimers with ERBB3 at a higher rate than the wild type ERBB2; Kancha et al. 2011, Bose et al. 2013 – indirect, higher kinase activity in the presence of ERBB3);<br>ERBB2 I767M (Ng et al. 2015 – indirect, catalytic activity induced by neuregulin-1 (NRG1));<br>ERBB2 D769H (Collier al. 2013 – direct, 3-fold increase in catalytic activity upon heterodimerization);<br>ERBB2 D769Y (Collier al. 2013 – direct, 3-fold increase in catalytic activity upon heterodimerization);<br>ERBB2 G776S (Fan et al. 2008 – indirect, trans-autophosphorylation increased in the presence of the mutant);<br>ERBB2 V777L (Croessmann et al. 2019 – direct, mutant forms heterodimers with ERBB3 at a higher rate than the wild type ERBB2; Kancha et al. 2011, Bose et al. 2013 – indirect, increased catalytic activity in the presence of neuregulin-activated ERBB3);<br>ERBB2 T798M (Rexer et al. 2013 – direct, co-immunoprecipitates with ERBB3; Kancha et al. 2011, Rexer et al. 2013 – indirect, trans-autophosphorylation in the presence of neuregulin-stimulated ERBB3);<br>ERBB2 V842I (Bose et al. 2013 – indirect, trans-autophosphorylation in the presence of ERBB3);<br>ERBB2 T862A (Kancha et al. 2011 - indirect, increased catalytic activity in the presence of neuregulin-activated ERBB3);<br>ERBB2 L869R (Hanker et al. 2017 – direct, heterodimerization may be increased in the presence of ERBB3 E928G mutant);<br>ERBB2 H878Y (Kancha et al. 2011 – indirect, activated in the presence of neuregulin-stimulated ERBB3);<br>ERBB2 L755_T759del (Bose et al. 2013 – indirect, ERBB3 phosphorylated in the presence of the mutant);<br>ERBB2 Y772_A775dup (Wang et al. 2006 - direct)<br><br>Heterodimerizaton of ERBB2 KD mutants with ERBB4 has not been tested and ERBB4 is shown as a heterodimerization candidate. <br><br>Heterodimerization properties of the following ERBB2 KD mutants have not been tested and they are annotated as candidates based on their substituted residue being identical to the substituted residue of functionally studied mutants and based on computational prediction of the pathogenicity of the mutation in COSMIC database:<br>ERBB2 L755M<br>ERBB2 L755W<br>ERBB2 D769N<br>ERBB2 V777E<br>ERBB2 V777M<br>ERBB2 T733I<br>ERBB2 T798I<br>ERBB2 V842E<br>ERBB2 L869Q<br>ERBB2 H878R<br>ERBB2 R896H<br>ERBB2 G776C<br>ERBB2 G776L<br>ERBB2 G776V

以下ERBB2激酶抑制突变体直接或间接地被证实与EGFR形成异源二聚体：<br><br>ERBB2 L755P（Kancha等，2011年，间接，在EGF刺激的EGFR存在下具有更高的催化活性）；<br>ERBB2 L755S（Kancha等，2011年，Bose等，2013年，间接，在EGFR存在下具有更高的激酶活性）；<br>ERBB2 I767M（Bose等，2013年，间接，ERBB2 I767M存在下EGFR发生磷酸化）；<br>ERBB2 D769H（Bose等，2013年，间接，在EGFR存在下发生跨自磷酸化）；<br>ERBB2 D769Y（Bose等，2013年，间接，在EGFR存在下发生跨自磷酸化）；<br>ERBB2 V777L（Kancha等，2011年，Bose等，2013年，间接，在EGF激活的EGFR存在下催化活性增加）；<br>ERBB2 G778_P780dup（Bose等，2013年，Suzawa等，2016年，Ogoshi等，2019年，间接，在EGFR存在下发生跨自磷酸化）；<br>ERBB2 T798M（Kancha等，2011年，Rexer等，2013年，间接，在EGF刺激的EGFR存在下发生跨自磷酸化）；<br>ERBB2 V842I（Bose等，2013年，间接，在EGFR存在下发生跨自磷酸化）；<br>ERBB2 T862A（Kancha等，2011年，间接，在EGF激活的EGFR存在下催化活性增加）；<br>ERBB2 H878Y（Kancha等，2011年，间接，在EGF刺激的EGFR存在下被激活）；<br>ERBB2 R896C（Bose等，2013年，间接，在EGFR存在下发生跨自磷酸化）；<br>ERBB2 L755_T759del（Bose等，2013年，间接，在突变体存在下EGFR发生磷酸化）；<br>ERBB2 Y772_A775dup（Wang等，2006年，直接）<br><br>以下ERBB2激酶抑制突变体直接或间接地被证实与ERBB3形成异源二聚体：<br><br>ERBB2 L755P（Kancha等，2011年，间接，在神经生长因子刺激的ERBB3存在下具有更高的催化活性）；<br>ERBB2 L755S（Croessmann等，2019年，直接，突变体与ERBB3形成异源二聚体的速率高于野生型ERBB2；Kancha等，2011年，Bose等，2013年，间接，在ERBB3存在下具有更高的激酶活性）；<br>ERBB2 I767M（Ng等，2015年，间接，由神经生长因子-1（NRG1）诱导的催化活性）；<br>ERBB2 D769H（Collier等，2013年，直接，异源二聚化后催化活性增加3倍）；<br>ERBB2 D769Y（Collier等，2013年，直接，异源二聚化后催化活性增加3倍）；<br>ERBB2 G776S（Fan等，2008年，间接，在突变体存在下跨自磷酸化增加）；<br>ERBB2 V777L（Croessmann等，2019年，直接，突变体与ERBB3形成异源二聚体的速率高于野生型ERBB2；Kancha等，2011年，Bose等，2013年，间接，在神经生长因子激活的ERBB3存在下催化活性增加）；<br>ERBB2 T798M（Rexer等，2013年，直接，与ERBB3共免疫沉淀；Kancha等，2011年，Rexer等，2013年，间接，在神经生长因子刺激的ERBB3存在下发生跨自磷酸化）；<br>ERBB2 V842I（Bose等，2013年，间接，在ERBB3存在下发生跨自磷酸化）；<br>ERBB2 T862A（Kancha等，2011年 - 间接，在神经生长因子激活的ERBB3存在下催化活性增加）；<br>ERBB2 L869R（Hanker等，2017年 - 直接，在ERBB3 E928G突变体存在下异源二聚化可能增加）；<br>ERBB2 H878Y（Kancha等，2011年 – 间接，在神经生长因子刺激的ERBB3存在下被激活）；<br>ERBB2 L755_T759del（Bose等，2013年 – 间接，在突变体存在下ERBB3发生磷酸化）；<br>ERBB2 Y772_A775dup（Wang等，2006年 - 直接）<br><br>ERBB2激酶抑制突变体与ERBB4的异源二聚化尚未进行测试，且ERBB4被列为异源二聚化候选者。<br><br>以下ERBB2激酶抑制突变体的异源二聚化特性尚未进行测试，它们被标注为候选者，其依据是它们替换的残基与功能研究突变体的替换残基相同，以及基于COSMIC数据库中对突变体致病性的计算预测：<br>ERBB2 L755M<br>ERBB2 L755W<br>ERBB2 D769N<br>ERBB2 V777E<br>ERBB2 V777M<br>ERBB2 T733I<br>ERBB2 T798I<br>ERBB2 V842E<br>ERBB2 L869Q<br>ERBB2 H878R<br>ERBB2 R896H<br>ERBB2 G776C<br>ERBB2 G776L<br>ERBB2 G776V