Advanced search×

Interactions between the three CIN85 SH3 domains and ubiquitin: implications for CIN85 ubiquitination.

Irina I Bezsonova, M Christine MC Bruce, Silke S Wiesner, Hong H Lin, Daniela D Rotin, and Julie D JD Forman-Kay

Biochemistry 47(34):8937-49 (2008) PMID 18680311

CIN85 is an adaptor protein linking the ubiquitin ligase Cbl and clathrin-binding proteins in clathrin-mediated receptor endocytosis. The SH3 domains of CIN85 bind to a proline-rich region of Cbl. Here we show that all three SH3 domains of CIN85 bind to ubiquitin. We also present a data-based structural model of the CIN85 SH3-C domain in complex with ubiquitin. In this complex, ubiquitin binds to the canonical interaction surface of the SH3 domain for proline-rich ligands and mimics the PPII helix, and we provide evidence that ubiquitin competes with these ligands for binding. We demonstrate that disruption of ubiquitin binding results in constitutive ubiquitination of CIN85 and an increased level of ubiquitination of EGFR in the absence of EGF stimulation. These results suggest that competition between Cbl and ubiquitin binding to CIN85 regulates Cbl function and EGFR endocytosis.

DOI: 10.1021/bi800439t
Version: za2963e q8zad q8zb7 q8zc4 q8zd4 q8ze4 q8zfc q8zg3

Similar articles you may find interesting…

  1. Cell surface heparan sulfate participates in CXCL1-induced signaling.
    Dingzhi D Wang, Jiqing J Sai, and Ann A Richmond

    Biochemistry 42(4):1071-7 (2003) PMID 12549928

    We show here that the CXCL1 maximal binding to CXCR2 expressed on HEK293 and CHO-K1 cells is dependent on the presence of cell surface HSPGs. The cell surface HSPGs on cells are required for CXCL1-induced PAK1 activation. Moreover, CXCL10 can inhibit CXCL1-induced PAK1 and ERK activation as well as...
    View PDF
  2. Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP sign...
    Ching-Shu Lai, Jong Hun Lee, ... Min-Hsiung Pan

    J Agric Food Chem 57(22):10990-8 (2009) PMID 19856917

    We investigated the inhibitory effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE(2). Treatme...
  3. SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner.
    Caleb B CB McDonald, Kenneth L KL Seldeen, ... Amjad A Farooq

    Biochemistry 48(19):4074-85 (2009) PMID 19323566 PMCID PMC2710136

    We demonstrate that while the nSH3 domain binds with affinities in the physiological range to all four sites containing PXpsiPXR motifs, designated S1, S2, S3, and S4, the cSH3 domain can only do so at the S1 site. Further scrutiny of these sites yields rationale for the recognition of various PXpsi...
    View PDF