Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P

Regul Pept. 2003 Mar 28;111(1-3):169-78. doi: 10.1016/s0167-0115(02)00288-4.

Abstract

Neurokinin 1 (NK-1) is a member of seven transmembrane G protein-coupled receptors. NK-1 interacts with peptides belonging to the tachykinin family and showed preference for substance P (SP). NK-1 is induced in bone marrow (BM) stroma. NK-1-SP interactions could lead to changes in the functions of lymphohematopoietic stem cell (LHSC). This report describes the cloning and characterization of a cDNA clone isolated after screening of three cDNA libraries with an NK-1-specific probe. Based on its expression, the cDNA clone was designated hematopoietic growth factor inducible neurokinin-1 type (HGFIN). Computational analyses predicted that HGFIN is transmembrane with the carboxyl terminal extracellular. Proteomic studies with purified HGFIN and SP showed noncovalent interactions. HGFIN-SP interactions were supported by transient expression of HGFIN in CHO cells. Transient expression of HGFIN in unstimulated BM fibroblasts led to the induction of endogenous NK-1. Since NK-1 expression in BM fibroblasts requires cell stimulation, these studies suggest that there might be intracellular crosstalk between NK-1 and HGFIN. Northern analyses with total RNA from different BM cell subsets showed that HGFIN was preferentially expressed in differentiated cells. This suggests that HGFIN might be involved in the maturation of LHSC. HGFIN was detected in several other tissues, but not in brain where NK-1 is constitutively expressed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Bone Marrow Cells / cytology
  • CHO Cells
  • Cell Differentiation / physiology
  • Cloning, Molecular
  • Cricetinae
  • DNA Probes
  • DNA, Complementary / genetics
  • Fibroblasts / metabolism
  • Hematopoietic Cell Growth Factors / metabolism*
  • Humans
  • Membrane Glycoproteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • RNA, Messenger / analysis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Nucleic Acid
  • Substance P / genetics
  • Substance P / metabolism*
  • Tissue Distribution

Substances

  • DNA Probes
  • DNA, Complementary
  • GPNMB protein, human
  • Hematopoietic Cell Growth Factors
  • Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Substance P

Associated data

  • GENBANK/AF322909