Human enhancer of filamentation 1, a novel p130 cas -like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae

Susan F. Law, Joanne Estojak, Baolin Wang, Tami Mysliwiec, Gary Kruh, Erica A. Golemis

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Abstract

Budding in Saccharomyces cerevisiae follows a genetically programmed pattern of cell division which can be regulated by external signals. On the basis of the known functional conservation between a number of mammalian oncogenes and antioncogenes with genes in the yeast budding pathway, we used enhancement of pseudohyphal budding in S. cerevisiae by human proteins expressed from a HeLa cDNA library as a morphological screen to identify candidate genes that coordinate cellular signaling and morphology. In this report, we describe the isolation and characterization of human enhancer of filamentation 1 (HEF1), an SH3-domain-containing protein that is similar in structure to p130 cas , a recently identified docking protein that is a substrate for phosphorylation by a number of oncogenic tyrosine kinases. In contrast to p130 cas , the expression of HEF1 appears to be tissue specific. Further, whereas p130 cas is localized predominantly at focal adhesions, immunofluorescence indicates that HEF1 localizes to both the cell periphery and the cell nucleus and is differently localized in fibroblasts and epithelial cells, suggesting a more complex role in cell signalling. Through immunoprecipitation and two-hybrid analysis, we demonstrate a direct physical interaction between HEFI and p130 cas , as well as an interaction of the SH3 domain of HEFI with two discrete proline-rich regions of focal adhesion kinase. Finally, we demonstrate that as with p130 cas , transformation with the oncogene v-abl results in an increase in tyrosine phosphorylation on HEFI, mediated by a direct association between HEFI and v-Abl. We anticipate that HEFI may prove to be an important linking element between extracellular signalling and regulation of the cytoskeleton.

Original languageEnglish (US)
Pages (from-to)3327-3337
Number of pages11
JournalMolecular and cellular biology
Volume16
Issue number7
DOIs
Publication statusPublished - Jan 1 1996

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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