Document Detail

Expression of the v-crk oncogene product in PC12 cells results in rapid differentiation by both nerve growth factor- and epidermal growth factor-dependent pathways.
MedLine Citation:
PMID:  7509449     Owner:  NLM     Status:  MEDLINE    
The transforming gene of the avian sarcoma virus CT10 encodes a fusion protein (p47gag-crk or v-Crk) containing viral Gag sequences fused to cellular sequences consisting primarily of Src homology regions 2 and 3 (SH2 and SH3 sequences). Here we report a novel function of v-Crk in the mammalian pheochromocytoma cell line, PC12, whereby stable expression of v-Crk induces accelerated differentiation, as assessed by induction of neurites following nerve growth factor (NGF) or basic fibroblast growth factor (bFGF) treatment compared with the effect in native PC12 cells. Surprisingly, however, these cells also develop extensive neurite processes after epidermal growth factor (EGF) stimulation, an event which is not observed in native PC12 cells. Following EGF or NGF stimulation of the v-CrkPC12 cells, the v-Crk protein itself became tyrosine phosphorylated within 1 min. Moreover, in A431 cells or TrkA-PC12 cells, which overexpress EGF receptors and TrkA, respectively, a GST-CrkSH2 fusion protein was indeed capable of binding these receptors in a phosphotyrosine-dependent manner, suggesting that v-Crk can directly couple to receptor tyrosine kinase pathways in PC12 cells. In transformed fibroblasts, v-Crk binds to specific tyrosine-phosphorylated proteins of p130 and paxillin. Both of these proteins are also complexed to v-Crk in PC12 cells, as evidenced by their coprecipitation with v-Crk in detergent lysates, suggesting that common effector pathways may occur in both cell types. However, whereas PC12 cellular differentiation can occur solely by overexpression of the v-Src or oncogenic Ras proteins, that induced by v-Crk requires a growth factor stimulatory signal, possibility in a two-step process.
B L Hempstead; R B Birge; J E Fajardo; R Glassman; D Mahadeo; R Kraemer; H Hanafusa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  14     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-03-25     Completed Date:  1994-03-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1964-71     Citation Subset:  IM    
Department of Hematology-Oncology, New York Hospital-Cornell Medical Center.
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MeSH Terms
Cell Differentiation*
Cell Division
Cytoskeletal Proteins / metabolism
Epidermal Growth Factor / physiology*
Fibroblast Growth Factor 2 / pharmacology
Insulin / pharmacology
Membrane Proteins / metabolism
Molecular Weight
Nerve Growth Factors / physiology*
Neurons / cytology*
Oncogene Protein v-crk
PC12 Cells
Phosphoproteins / chemistry,  metabolism
Proteins / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-crk
Receptors, Nerve Growth Factor / metabolism
Retroviridae Proteins, Oncogenic / physiology*
Signal Transduction
Tyrosine / analogs & derivatives,  metabolism
Grant Support
Reg. No./Substance:
0/Cytoskeletal Proteins; 0/Membrane Proteins; 0/Nerve Growth Factors; 0/Oncogene Protein v-crk; 0/Paxillin; 0/Phosphoproteins; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-crk; 0/Receptors, Nerve Growth Factor; 0/Retroviridae Proteins, Oncogenic; 103107-01-3/Fibroblast Growth Factor 2; 11061-68-0/Insulin; 21820-51-9/Phosphotyrosine; 55520-40-6/Tyrosine; 62229-50-9/Epidermal Growth Factor

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