High impact information on Itsn1

• EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP [1].
• This inhibitory mechanism seems to act through steric hindrance of Cdc42 binding by an intramolecular interaction between the intersectin 1L SH3 domain region and the adjacent DH domain [2].
• The dual role of the SH3 domains in endocytosis and repression of exchange activity suggests that the intersectin 1L exchange activity is regulated by endocytosis [2].
• Intersectin 1L is a scaffolding protein involved in endocytosis that also has guanine nucleotide exchange activity for Cdc42 [2].
• Distinct functional interactions of human Skn-1 isoforms with Ese-1 during keratinocyte terminal differentiation [3].

Biological context of Itsn1

• Intersectin 1L guanine nucleotide exchange activity is regulated by adjacent src homology 3 domains that are also involved in endocytosis [2].
• In addition, we identified expressed sequence tags that encode a second isoform of EHSH1, called EHSH2 [4].
• In yeast two-hybrid screens for proteins that bind to SNAP-25 and may be involved in exocytosis, we isolated a protein called EHSH1 (for EH domain/SH3 domain-containing protein) [4].
• Alternative splicing of mammalian Intersectin 1: domain associations and tissue specificities [5].
• Activation of the murine type II transforming growth factor-beta receptor gene: up-regulation and function of the transcription factor Elf-3/Ert/Esx/Ese-1 [6].

Anatomical context of Itsn1

• In platelet-derived growth factor-stimulated Swiss 3T3 cells, intersectin co-localizes with CdGAP and inhibits its GAP activity toward Rac1 [7].

Associations of Itsn1 with chemical compounds

• Thus, we propose a model in which intersectin binding results in a change of CdGAP conformation involving the proline-rich domain that leads to the inhibition of its GAP activity [7].
• Cloning of full-length cDNAs revealed that EHSH1 is composed of an N-terminal region with two EH domains, a central region that is enriched in lysine, leucine, glutamate, arginine, and glutamine (KLERQ domain), and a C-terminal region comprised of five SH3 domains [4].

Analytical, diagnostic and therapeutic context of Itsn1

• Yeast two-hybrid assays have revealed that Ese1 EH and SH3 domains bind epsin family proteins and dynamin, respectively [8].

References