The Cbl family proteins: Ring leaders in regulation of cell signaling

摘要: The proto-oncogenic protein c-Cbl was discovered as the cellular form of v-Cbl, a retroviral transforming protein. This followed over years by important discoveries, which identified and other Cbl-family proteins key players in several signaling pathways. has donned role multivalent adaptor protein, capable interacting with plethora proteins, been shown to positively influence certain biological processes. identity an E3 ubiquitin ligase unveiled existence negative regulatory pathway involved maintaining homeostasis tyrosine kinase (PTK) signaling. Recent have also seen emergence novel regulators Cbl, provided further insights into complexity Cbl-influenced review will endeavor provide summary current studies focused on effects Cbl various processes mechanism these effects. major sections are follows: Structure genomic organization proteins; Phosphorylation Cbl; Interactions Localization Mechanism Cbl: (a) Ubiquitylation-dependent events: section elucidates Cbl-mediated downregulation EGFR details PTK non-PTKs targeted Cbl. In addition, it addresses functional requirements for Ubiquitin activity regulation PTKs, (b) Adaptor functions: discusses mechanisms functions mitogen-activated (MAPK) activation, insulin signaling, Ras-related 1 (Rap1), PI-3' Rho-family GTPases cytoskeleton; Biological gives account diverse includes transformation, T-cell thymus development, B-cell mast-cell degranulation, macrophage functions, bone neurite growth, platelet muscle degeneration, bacterial invasion; Conclusions perspectives.