Background information
SH3KBP1 belongs to the CIN85/CMS family of adaptor molecules, characterized by containing three N-terminal Src homology domains, a proline rich region and a C-terminal coiled-coil domain. The different members of the family orchestrate a network involved in dowregulation and degradation of recpetor tyrosine kinases. SH3KBP1 is involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through a association with CBL and endophilins. In the case of EGF receptor turnover, its activation involves recruitment of SH3KBP1- endophilin complexes to mediate internalization. Once internalized, RTKs are delivered into the endosomal compartment where receptors get sorted for either recycling back to the cell surface or are targeted to lysosomes for degradation. Alternate splicing results in multiple transcript variants.
