文摘
Kaposi's sarcoma-associated herpesvirus, also known as human herpesvirus 8, is closelyassociated with several cancers including Kaposi's sarcoma, primary effusion lymphoma, and multicentricCastleman's disease. The rightmost end of the KSHV genome encodes a protein, K15, with multiplemembrane-spanning segments and an intracellular carboxy-terminal tail that contains several conservedmotifs with the potential to recruit interaction domains (i.e., SH2, SH3, TRAF) of host cell proteins. K15has been implicated in downregulating B cell receptor (BCR) signaling through its conserved motifs andmay thereby play a role in maintaining viral latency and/or preventing apoptosis of the infected B cells.However, K15's mode of action is largely unknown. We have used mass spectrometry, domain and peptidearrays, and surface plasmon resonance to identify binding partners for a conserved proline-rich sequence(PPLP) in the K15 cytoplasmic tail. We show that the PPLP motif selectively binds the SH3-C domainof an endocytic adaptor protein, Intersectin 2 (ITSN2). This interaction can be observed both in vitro andin cells, where K15 and ITSN2 colocalize to discrete compartments within the B cell. The ability of K15to associate with ITSN2 suggests a new role for the K15 viral protein in intracellular protein trafficking.