Recognition sequences and structural elements contribute to shedding susceptibility of membrane proteins.

摘要: Although regulated ectodomain shedding affects a large panel of structurally and functionally unrelated proteins, little is known about the mechanisms controlling this process. Despite lack sequence similarities around cleavage sites, most proteins are shed in response to stimulation protein kinase C by phorbol esters. The signal-transducing receptor subunit gp130 not substrate machinery. We generated several chimaeric tumour necrosis factor alpha (TNF-alpha), transforming growth (TGF-alpha) interleukin 6 (IL-6R), which be subject shedding. By exchanging small peptide sequences for cleavage-site peptides TNF-alpha, TGF-alpha IL-6R we showed that these short conferred susceptibility spontaneous phorbol-ester-induced gp130. Importantly, were functional, as shown phosphorylation activation signal transduction activators transcription 3 ('STAT3') on with cytokine. To investigate minimal requirements shedding, truncated inserted into resulting chimaeras susceptible same pattern observed containing complete site. Surprisingly, could also generate cleavable juxtamembrane corresponding region leukaemia inhibitory ('LIF') receptor, like or Thus it seems there no consensus sequence. speculate structural changes allow access protease membrane-proximal region, leading protein.