Capitulo de libro
SIGNALING PATHWAYS COUPLED TO ACTIVATION OF THE KININ B1 RECEPTOR
ADVANCES IN PROTEIN KINASES
Registro en:
11090292
978953510633-3
Autor
Bhoola, Kanti Daya
Ehrenfeld Slater, Ingrid Pamela
Figueroa Valverde, Carlos Dario
Matus Velasquez, Carola Elizabeth
Institución
Resumen
Kinins are a group of bioactive peptides, which are formed by an endogenous enzymatic
cascade consisting of precursor substrates called kininogens and the proteolytic kallikrein
enzymes (kininogenases). So far, two kinin-releasing enzymes (kininogenases) have been
characterized, plasma (hKB1/LKLB1) and tissue (hK1/KLK1) kallikreins (Fig. 1). Both
enzymes are serine proteases that are found in glandular cells, neutrophils, and biological
fluids. Kininogens are multifunctional proteins involved in cascade reactions during
inflammation (Bhoola et al., 1992), and more recently in carcinogenesis (Bhoola et al., 1992;
2001; Leeb-Lundberg et al., 2005). Kinins namely bradykinin (BK) and kallidin (Lys-BK) are
among the most potent pro-inflammatory vasoactive peptides generated during tissue
injury and noxious stimulation. BK and Lys-BK undergo metabolic degradation at a variable
rate by amino-, carboxy- and endopeptidases found in tissues and biological fluids. The
most physiologically relevant enzymes are carboxypeptidase N (from plasma) and
carboxypeptidase M (from cell membranes), which remove the carboxy-terminal Arg
present at end of the kinin molecule, resulting in the formation of the active metabolites desArg9-BK
(DBK) and des-Arg10-kallidin, known also as Lys-des-Arg9-BK (LDBK) (Fig. 1).
Furthermore, neutral endopeptidase 24.11 (CD10, enkephalinase) and angiotensin I
converting enzyme, act as dipeptidyl carboxypeptidases by removing the dipeptide Phe8-
Arg9 from the carboxy terminus end of BK or Lys-BK (Couture et al., 2004). It is important to
mention that endopeptidase 24.15 and angiotensin I converting enzyme cleave the dipeptide
Ser6-Pro7 from bradykinin 1-7 (BK1-7) to produce bradykinin 1-5 (BK1-5), one of the final
metabolites of BK and DBK that possesses the longer half-life of this peptide family. The
half-life of kinins depends on the rate and site of destruction, most rapid in the circulation,
but less so in the extracellular fluid space and by cells. Actually, in plasma the half-life of BK
and LDBK is short (15 to 20 sec) whereas BK1-5, considered in the past an inactive fragment,
is considered to have a half-life of 86 to 101 min (Shima et al., 1992; Murphey et al., 2000;
2006; Morinelli et al., 2002). Kinins are a group of bioactive peptides, which are formed by an endogenous enzymatic
cascade consisting of precursor substrates called kininogens and the proteolytic kallikrein
enzymes (kininogenases). So far, two kinin-releasing enzymes (kininogenases) have been
characterized, plasma (hKB1/LKLB1) and tissue (hK1/KLK1) kallikreins (Fig. 1). Both
enzymes are serine proteases that are found in glandular cells, neutrophils, and biological
fluids. Kininogens are multifunctional proteins involved in cascade reactions during
inflammation (Bhoola et al., 1992), and more recently in carcinogenesis (Bhoola et al., 1992;
2001; Leeb-Lundberg et al., 2005). Kinins namely bradykinin (BK) and kallidin (Lys-BK) are
among the most potent pro-inflammatory vasoactive peptides generated during tissue
injury and noxious stimulation. BK and Lys-BK undergo metabolic degradation at a variable
rate by amino-, carboxy- and endopeptidases found in tissues and biological fluids. The
most physiologically relevant enzymes are carboxypeptidase N (from plasma) and
carboxypeptidase M (from cell membranes), which remove the carboxy-terminal Arg
present at end of the kinin molecule, resulting in the formation of the active metabolites desArg9-BK
(DBK) and des-Arg10-kallidin, known also as Lys-des-Arg9-BK (LDBK) (Fig. 1).
Furthermore, neutral endopeptidase 24.11 (CD10, enkephalinase) and angiotensin I
converting enzyme, act as dipeptidyl carboxypeptidases by removing the dipeptide Phe8-
Arg9 from the carboxy terminus end of BK or Lys-BK (Couture et al., 2004). It is important to
mention that endopeptidase 24.15 and angiotensin I converting enzyme cleave the dipeptide
Ser6-Pro7 from bradykinin 1-7 (BK1-7) to produce bradykinin 1-5 (BK1-5), one of the final
metabolites of BK and DBK that possesses the longer half-life of this peptide family. The
half-life of kinins depends on the rate and site of destruction, most rapid in the circulation,
but less so in the extracellular fluid space and by cells. Actually, in plasma the half-life of BK
and LDBK is short (15 to 20 sec) whereas BK1-5, considered in the past an inactive fragment,
is considered to have a half-life of 86 to 101 min (Shima et al., 1992; Murphey et al., 2000;
2006; Morinelli et al., 2002). Kinins are a group of bioactive peptides, which are formed by an endogenous enzymatic
cascade consisting of precursor substrates called kininogens and the proteolytic kallikrein
enzymes (kininogenases). So far, two kinin-releasing enzymes (kininogenases) have been
characterized, plasma (hKB1/LKLB1) and tissue (hK1/KLK1) kallikreins (Fig. 1). Both
enzymes are serine proteases that are found in glandular cells, neutrophils, and biological
fluids. Kininogens are multifunctional proteins involved in cascade reactions during
inflammation (Bhoola et al., 1992), and more recently in carcinogenesis (Bhoola et al., 1992;
2001; Leeb-Lundberg et al., 2005). Kinins namely bradykinin (BK) and kallidin (Lys-BK) are
among the most potent pro-inflammatory vasoactive peptides generated during tissue
injury and noxious stimulation. BK and Lys-BK undergo metabolic degradation at a variable
rate by amino-, carboxy- and endopeptidases found in tissues and biological fluids. The
most physiologically relevant enzymes are carboxypeptidase N (from plasma) and
carboxypeptidase M (from cell membranes), which remove the carboxy-terminal Arg
present at end of the kinin molecule, resulting in the formation of the active metabolites desArg9-BK
(DBK) and des-Arg10-kallidin, known also as Lys-des-Arg9-BK (LDBK) (Fig. 1).
Furthermore, neutral endopeptidase 24.11 (CD10, enkephalinase) and angiotensin I
converting enzyme, act as dipeptidyl carboxypeptidases by removing the dipeptide Phe8-
Arg9 from the carboxy terminus end of BK or Lys-BK (Couture et al., 2004). It is important to
mention that endopeptidase 24.15 and angiotensin I converting enzyme cleave the dipeptide
Ser6-Pro7 from bradykinin 1-7 (BK1-7) to produce bradykinin 1-5 (BK1-5), one of the final
metabolites of BK and DBK that possesses the longer half-life of this peptide family. The
half-life of kinins depends on the rate and site of destruction, most rapid in the circulation,
but less so in the extracellular fluid space and by cells. Actually, in plasma the half-life of BK
and LDBK is short (15 to 20 sec) whereas BK1-5, considered in the past an inactive fragment,
is considered to have a half-life of 86 to 101 min (Shima et al., 1992; Murphey et al., 2000;
2006; Morinelli et al., 2002). Kinins are a group of bioactive peptides, which are formed by an endogenous enzymatic
cascade consisting of precursor substrates called kininogens and the proteolytic kallikrein
enzymes (kininogenases). So far, two kinin-releasing enzymes (kininogenases) have been
characterized, plasma (hKB1/LKLB1) and tissue (hK1/KLK1) kallikreins (Fig. 1). Both
enzymes are serine proteases that are found in glandular cells, neutrophils, and biological
fluids. Kininogens are multifunctional proteins involved in cascade reactions during
inflammation (Bhoola et al., 1992), and more recently in carcinogenesis (Bhoola et al., 1992;
2001; Leeb-Lundberg et al., 2005). Kinins namely bradykinin (BK) and kallidin (Lys-BK) are
among the most potent pro-inflammatory vasoactive peptides generated during tissue
injury and noxious stimulation. BK and Lys-BK undergo metabolic degradation at a variable
rate by amino-, carboxy- and endopeptidases found in tissues and biological fluids. The
most physiologically relevant enzymes are carboxypeptidase N (from plasma) and
carboxypeptidase M (from cell membranes), which remove the carboxy-terminal Arg
present at end of the kinin molecule, resulting in the formation of the active metabolites desArg9-BK
(DBK) and des-Arg10-kallidin, known also as Lys-des-Arg9-BK (LDBK) (Fig. 1).
Furthermore, neutral endopeptidase 24.11 (CD10, enkephalinase) and angiotensin I
converting enzyme, act as dipeptidyl carboxypeptidases by removing the dipeptide Phe8-
Arg9 from the carboxy terminus end of BK or Lys-BK (Couture et al., 2004). It is important to
mention that endopeptidase 24.15 and angiotensin I converting enzyme cleave the dipeptide
Ser6-Pro7 from bradykinin 1-7 (BK1-7) to produce bradykinin 1-5 (BK1-5), one of the final
metabolites of BK and DBK that possesses the longer half-life of this peptide family. The
half-life of kinins depends on the rate and site of destruction, most rapid in the circulation,
but less so in the extracellular fluid space and by cells. Actually, in plasma the half-life of BK
and LDBK is short (15 to 20 sec) whereas BK1-5, considered in the past an inactive fragment,
is considered to have a half-life of 86 to 101 min (Shima et al., 1992; Murphey et al., 2000;
2006; Morinelli et al., 2002). FONDECYT 384 FONDECYT