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PMID: 8321240 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Both the SH2 and SH3 domains of human CRK protein are required for neuronal differentiation of PC12 cells.

Molecular and cellular biology ·Vol. 13 ·No. 7 ·1993-07-00 ·Pages 4409-15

Tanaka S, Hattori S, Kurata T, Nagashima K, Fukui Y, Nakamura S, Matsuda M

Abstract

Human CRK protein is a homolog of the chicken v-crk oncogene product and consists mostly of src homology region 2 (SH2) and SH3, which are shared by many proteins, in particular those involved in signal transduction. SH2 has been shown to bind specifically to phosphotyrosine-containing peptides. We report here that both SH2 and SH3 are required for signaling from CRK protein. Microinjection of the CRK protein induced neurite formation of rat pheochromocytoma cell line PC12. This activity was abolished by mutation of the CRK protein in either SH2 or SH3. The neuronal differentiation induced by the CRK protein was blocked by an excess amount of peptides containing CRK SH3. Moreover, we identified three proteins, of 118, 125, and 136 kDa, which bound specifically to CRK SH3. The CRK-induced neuronal differentiation was also suppressed by monoclonal antibodies against either CRK SH2 or p21ras. These results suggest that both SH2 and SH3 of the CRK protein mediate specific protein-protein binding and that the resulting multimolecular complex generates a signal for neurite differentiation through activation of p21ras.

MeSH Terms
Amino Acid Sequence Animals Cell Differentiation Humans Immunohistochemistry Molecular Sequence Data Neurites/metabolism Neurons/cytology Oncogene Protein v-crk PC12 Cells Retroviridae Proteins, Oncogenic/chemistry,metabolism
Chemicals
Oncogene Protein v-crk Retroviridae Proteins, Oncogenic
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Tanaka S
Department of Pathology, National Institute of Health, Tokyo, Japan.
Hattori S
Kurata T
Nagashima K
Fukui Y
Nakamura S
Matsuda M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.7.4409-4415.1993
Published
1993-07-00
Pages
4409-15
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360008
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.7.4409-4415.1993 PMC Full Text View journal details
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