Interactions of ErbB4 and Kap1 Connect the Growth Factor and DNA Damage Response Pathways

Overview

Journal Mol Cancer Res

Specialty Cell Biology

Date 2010 Sep 23

PMID 20858735

Citations 18

Authors

Maureen Gilmore-Hebert

Rajani Ramabhadran

David F Stern

Affiliations

Soon will be listed here.

Abstract

ErbB4 is unusual among receptor tyrosine kinases because some isoforms can be efficiently cleaved at the plasma membrane to release a soluble intracellular domain. The cleavage product has high kinase activity and homes to the nucleus. A screen for proteins that associate with the ErbB4 intracellular domain identified candidate interactors including ITCH, WWP2, Nucleolin, and Krab-associated protein 1 (Kap1). Kap1 binds to multiple isoforms of ErbB4 but does not require ErbB4 kinase activity for binding, nor is it an ErbB4 substrate. Kap1 reduces ERBB4 transcription and either directly or indirectly modulates the expression of genes that are themselves regulated by ErbB4. Upregulation of ErbB4 and suppression of MDM2 jointly enhance and accelerate the accumulation of p21(CIP1) in response to DNA damage. Overall, these findings further substantiate the role of ErbB4 in conjoint regulation of growth factor signaling and DNA damage responses.

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