Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was liberated from purified chromogranin A. Of 15

All patients with pheochromocytomas should be screened for MEN-2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. All patients in families with MEN-2 or von Hippel-Lindau disease should be screened for pheochromocytoma, even if they are asymptomatic.

We conclude that catestatin is diminished early in the course of development of hypertension, even in the normotensive offspring of patients with the disease. Low catestatin predicts augmented adrenergic pressor responses, suggesting a mechanism whereby diminished catestatin might increase the risk for later development of hypertension.

Activation of plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin, is markedly promoted when plasminogen is bound to cell surfaces, arming cells with the broad spectrum proteolytic activity of plasmin. In addition to its role in thrombolysis, cell surface plasmin facilitates a wide array of physiologic and pathologic processes. Carboxypeptidase B-sensitive plasminogen binding sites promote plasminogen activation on eukaryotic cells. However, no integral membrane plasminogen receptors exposing carboxyl terminal basic residues on cell surfaces have been identified. Here we use the exquisite sensitivity of multidimensional protein identification technology and an inducible progenitor cell line to identify a novel differentiation-induced integral membrane plasminogen receptor that exposes a C-terminal lysine on the cell surface, Plg-R KT (C9orf46 homolog). Plg-R KT was highly colocalized on the cell surface with the urokinase receptor, uPAR.Our data suggest that Plg-R KT also interacts directly with tissue plasminogen activator. Furthermore, Plg-R KT IntroductionLocalization of plasminogen on cell surfaces is a crucial control point for positive regulation of cell surface plasmin proteolytic activity that facilitates both physiologic and pathologic processes, 1,2 including macrophage recruitment during the inflammatory response, [3][4][5][6] tissue remodeling, 7 wound healing, 8,9 tumor cell invasion and metastasis, 10-12 skeletal myogenesis, 13 neuroendocrine prohormone processing, 14,15 and neurite outgrowth. 16,17 Cell surface plasminogen binding sites promote plasminogen activation by reducing the Km (11-to 60-fold) for plasminogen activation. [18][19][20][21][22][23][24] Active plasmin also associates with the cell surface, where its activity is protected from inhibitors. 25,26 Plasminogen binding sites are very broadly distributed on both eukaryotic and prokaryotic cells. 27 Of the many eukaryotic cells examined to date, only erythrocytes do not bind plasminogen. 28 The interactions of plasminogen with eukaryotic cells are mediated by lysine binding sites within the disulfide-bonded kringle domains of plasminogen. 18,29 Therefore, plasminogen binding to eukaryotic cells is blocked in the presence of lysine and lysine analogs, including ⑀-aminocaproic acid (EACA). 27 Because most cell types have a very high capacity for plasminogen, no single molecule can account for the entire plasminogen binding capacity of a given cell type. 27 However, a subset of plasminogen binding proteins exposing C-terminal basic residues on cell surfaces are predominantly responsible for the ability of eukaryotic cells to enhance plasminogen activation because carboxypeptidase B (CpB) treatment abrogates cell surface-dependent plasminogen activation. 24 Correspondingly, plasminogen-dependent macrophage recruitment in vivo is mediated by CpB-sensitive plasminogen receptors, and plasminogen binding to recruited macrophages is increased, compared with peripheral blood monocytes. 6,30 Therefore, we probed the monocyte ...