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PMID: 1656221 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1.

Molecular and cellular biology ·Vol. 11 ·No. 10 ·1991-10-00 ·Pages 5068-78

Mohammadi M, Honegger AM, Rotin D, Fischer R, Bellot F, Li W, Dionne CA, Jaye M, Rubinstein M, Schlessinger J

Abstract

Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR; encoded by the flg gene) and other receptors with tyrosine kinase activity. It has been demonstrated that the src homology region 2 (SH2 domain) of PLC-gamma and of other signalling molecules such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85 direct their binding toward tyrosine-autophosphorylated regions of the epidermal growth factor or platelet-derived growth factor receptor. In this report, we describe the identification of Tyr-766 as an autophosphorylation site of flg-encoded FGFR by direct sequencing of a tyrosine-phosphorylated tryptic peptide isolated from the cytoplasmic domain of FGFR expressed in Escherichia coli. The same phosphopeptide was found in wild-type FGFR phosphorylated either in vitro or in living cells. Like other growth factor receptors, tyrosine-phosphorylated wild-type FGFR or its cytoplasmic domain becomes associated with intact PLC-gamma or with a fusion protein containing the SH2 domain of PLC-gamma. To delineate the site of association, we have examined the capacity of a 28-amino-acid tryptic peptide containing phosphorylated Tyr-766 to bind to various constructs containing SH2 and other domains of PLC-gamma. It is demonstrated that the tyrosine-phosphorylated peptide binds specifically to the SH2 domain but not to the SH3 domain or other regions of PLC-gamma. Hence, Tyr-766 and its flanking sequences represent a major binding site in FGFR for PLC-gamma. Alignment of the amino acid sequences surrounding Tyr-766 with corresponding regions of other FGFRs revealed conserved tyrosine residues in all known members of the FGFR family. We propose that homologous tyrosine-phosphorylated regions in other FGFRs also function as binding sites for PLC-gamma and therefore are involved in coupling to phosphatidylinositol breakdown.

Related Genes
f1g
MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Cloning, Molecular Escherichia coli/metabolism Filaggrin Proteins Humans Molecular Sequence Data Phosphorylation Precipitin Tests Receptors, Cell Surface/metabolism Receptors, Fibroblast Growth Factor Sequence Alignment T-Phages/metabolism Type C Phospholipases/metabolism Tyrosine/metabolism
Chemicals
FLG protein, human Filaggrin Proteins Receptors, Cell Surface Receptors, Fibroblast Growth Factor Tyrosine Type C Phospholipases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Mohammadi M
Department of Pharmacology, New York University Medical Center, New York 10016.
Honegger A M
Rotin D
Fischer R
Bellot F
Li W
Dionne C A
Jaye M
Rubinstein M
Schlessinger J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.10.5068-5078.1991
Published
1991-10-00
Pages
5068-78
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361508
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.11.10.5068-5078.1991 PMC Full Text View journal details
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