Nerve growth factor stimulates the tyrosine phosphorylation of endogenous Crk-II and augments its association with p130Cas in PC-12 cells.
The cellular homologs of the v-Crk oncogene product consist primarily of Src homology region 2 (SH2) and 3 (SH3) domains. v-Crk overexpression causes cell transformation and elevation of tyrosine phosphorylation in fibroblasts and accelerates differentiation of PC-12 cells in response to nerve growth factor (NGF). To further explore the role of Crk in NGF-induced PC-12 cell differentiation, we found that both NGF and epidermal growth factor stimulate the tyrosine phosphorylation of endogenous Crk II. Moreover, hormone stimulation enhanced the specific association of Crk proteins with the tyrosine-phosphorylated p130Cas, the major phosphotyrosine-containing protein in cells transformed with v-Crk. This interaction is mediated by the SH2 domain of Crk and can be inhibited with a phosphopeptide containing the Crk-SH2 binding motif. Furthermore, the Crk-SH2 domain binds tyrosine-phosphorylated paxillin, a cytoskeletal protein, following treatment of PC-12 cells with NGF or epidermal growth factor. These data suggest that Crk functions in a number of signaling processes in PC-12 cells.
Ribon
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Department of Physiology, University of Michigan School of Medicine, Ann Arbor, 48109, USA.
Saltiel
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AR
D000310:Adrenal Gland Neoplasms; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D050719:Crk-Associated Substrate Protein; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D050736:Oncogene Protein v-crk; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010673:Pheochromocytoma; D010748:Phosphopeptides / Q000737:chemistry / Q000302:isolation & purification; D010750:Phosphoproteins / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D015682:Retroviridae Proteins, Oncogenic / Q000302:isolation & purification / Q000378:metabolism*; D014443:Tyrosine
C493843:Bcar1 protein, rat; D050719:Crk-Associated Substrate Protein; D009414:Nerve Growth Factors; D050736:Oncogene Protein v-crk; D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D015682:Retroviridae Proteins, Oncogenic; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors