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Phosphatidylinositol 3′‐kinase associates with p145c‐kit as part of a cell type characteristic multimeric signalling complex.
Author(s) -
Shearman M.S.,
Herbst R.,
Schlessinger J.,
Ullrich A.
Publication year - 1993
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1993.tb06060.x
Subject(s) - biology , phosphatidylinositol , kinase , microbiology and biotechnology , signalling , type (biology) , cell type , signal transduction , biochemistry , cell , genetics , computational biology , ecology
p145c‐kit is expressed in cell lineages of diverse origin and appears to regulate distinct cell type characteristic functions. Independent mutations at the murine Dominant White Spotting (W) locus result in the alteration of p145c‐kit tyrosine kinase activity and signalling potential, which differentially affects melanocyte migration, germ cell regeneration and hematopoietic cell differentiation. Molecules that may be involved in mediation and definition of p145c‐kit signalling pathways were investigated in cell lines of hematopoietic, melanogenic and central nervous system origin. High‐affinity association of endogenous cellular proteins with activated p145c‐kit was limited to a characteristic set of molecules that correlated with the presence of phosphatidylinositol (PtdIns) 3′‐kinase activity. The observed association pattern of proteins was cell type characteristic, and all of the proteins were displaced from the receptor by competition with excess receptor binding subunit of PtdIns 3′‐kinase. Our data indicate that PtdIns 3′‐kinase associates with p145c‐kit as part of a multimeric signalling complex, and suggest that the cell type characteristic composition of this complex influences the signalling potential of p145c‐kit in the diverse cell types in which it is expressed and thereby defines its cell type‐specific functions.